NEURO <4> Database EMBASE Accession Number 2006029823 Authors Jacob C.P. Muller J. Schmidt M. Hohenberger K. Gutknecht L. Reif A. Schmidtke A. Mossner R. Lesch K.P. Institution (Jacob, Schmidt, Hohenberger, Gutknecht, Reif, Schmidtke, Mossner, Lesch) Clinical and Molecular Psychobiology, Department of Psychiatry and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany. (Muller) Differential and Personality Psychology, Institute of Psychology II, Technical University of Dresden, Dresden, Germany. (Jacob) Department of Psychiatry and Psychotherapy, University of Wuerzburg, Fuechsleinstrasse 15, 97080 Wuerzburg, Germany. Country of Publication United Kingdom Title Cluster B personality disorders are associated with allelic variation of monoamine oxidase A activity. Source Neuropsychopharmacology. 30(9)(pp 1711-1718), 2005. Date of Publication: Sep 2005. Abstract Genetic variants of the monoamine oxidase A (MAOA) have been associated with aggression-, anxiety-, and addiction-related behavior in several nonclinical and clinical populations. Here, we investigated the influence of allelic variation of MAOA activity on aggression-related personality traits and disease risk in patients with personality disorders. Personality disorders were diagnosed with the Structured Clinical Interview of DSM-IV and were allocated to cluster A, B, and C. Personality features were assessed by the revised NEO Personality Inventory and the Tridimensional Personality Questionnaire. The genotype of the MAOA gene-linked polymorphic region (MAOA-LPK) was determined in 566 patients with personality disorders and in 281 healthy controls. MAOA genotype was significantly associated with cluster B personality disorders (chi² = 7.77, p = 0.005, df = 1) but not with cluster C personality disorders. In total, 26.0% of cluster B patients were hemi- or homozygous for the low-activity variant of the MAOA genotype, compared to 16.4% in the control group. Associations between MAOA variants and personality domains related to impulsivity and aggressiveness were inconsistent. Our findings further support the notion that allelic variation of MAOA activity contributes modestly to the balance of hyper- (impulsive- aggressive) and hyporeactive (anxious-depressive) traits. copyright 2005 Nature Publishing Group. All rights reserved. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 30 Issue Part 9 Page 1711-1718 Year of Publication 2005 Date of Publication Sep 2005

NEURO <11> Database EMBASE Accession Number 2006002334 Authors Salt T.E. Institution (Salt) University College London, Institute of Opthalmology, Department of Visual Science, 11-43 Bath Street, London EC1V 9EL, United Kingdom. Country of Publication United Kingdom Title Metabotropic Glutamate Receptors - Fifth International Meeting. 18-23 September 2005, Taormina, Italy. Source IDrugs. 8(12)(pp 971-973), 2005. Date of Publication: Dec 2005. Abstract There have been notable developments in the field of mGluRs in recent years including the identification of new compounds, novel mechanisms of action and potential therapeutic indications for drugs acting at one or more of the eight mGluRs. There is clearly great interest from both academic and industrial laboratories in the development of mGluR modulating compounds, which is reflected in the continued growth and vitality of this meeting. The many new positive and negative allosteric modulators hold much promise for the treatment of anxiety disorders, schizophrenia and addiction, and offer hope for the development of entirely new classes of clinically useful drugs. The initial clinical findings reported for group II agonists are particularly promising in this regard. The abstracts of this meeting are published as part of a special edition of Neuropharmacology (2005) 49(Suppl 1). copyright The Thomson Corporation. ISSN 1369-7056 Publication Type Journal: Conference Paper Journal Name IDrugs Volume 8 Issue Part 12 Page 971-973 Year of Publication 2005 Date of Publication Dec 2005

NEURO <17> Database EMBASE Accession Number 2005578350 Authors Coggeshall R.E. Institution (Coggeshall) Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-1069, United States. Country of Publication United Kingdom Title Fos, nociception and the dorsal horn. Source Progress in Neurobiology. 77(5)(pp 299-352), 2005. Date of Publication: Dec 2005. Abstract The protooncogene c-fos is rapidly activated after noxious stimuli to express the protein Fos in spinal dorsal horn neurons that are in the 'correct' locations for nociceptive information transfer. As such, therefore, mapping Fos expression in these neurons is at present the best global marker for efficiently locating populations of neurons in the awake animal that respond to nociceptive input. This allows, among other things, precise behavioral measurements to be correlated with Fos expression. Two arenas where mapping dorsal horn Fos expression has made a major impact are in the anatomy of nociceptive systems and as a useful assay for the analgesic properties of various therapeutic regimens. Also Fos expression is the only way to map populations of neurons that are responding to non-localized input such as withdrawal after addiction and vascular occlusion. Another insight is that it shows a clear activation of neurons in superficial 'pain-processing' laminae by innocuous stimuli after nerve lesions, a finding that presumably bears on the allodynia that often accompanies these lesions. It is to be understood, however, that the Fos localizations are not sufficient unto themselves, but the major function of these studies is to efficiently locate populations of cells in nociceptive pathways so that powerful anatomic and physiologic techniques can be brought to bear efficiently. Thus, the purpose of this review is to summarize the studies whose numbers are geometrically expanding that deal with Fos in the dorsal horn and the conclusions therefrom. copyright 2005 Elsevier Ltd. All rights reserved. ISSN 0301-0082 Publication Type Journal: Review Journal Name Progress in Neurobiology Volume 77 Issue Part 5 Page 299-352 Year of Publication 2005 Date of Publication Dec 2005

NEURO <28> Database EMBASE Accession Number 2005566619 Authors Spanagel R. Heilig M. Institution (Spanagel) Department of Psychopharmacology, Central Institute of Mental Health (CIMH), University of Heidelberg, Mannheim 68159, Germany. (Heilig) Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, MD, United States. Country of Publication United Kingdom Title Addiction and its brain science. Source Addiction. 100(12)(pp 1813-1822), 2005. Date of Publication: Dec 2005. Abstract Aims: To illustrate how modern neurobiological approaches will help to identify the neurocircuits and genes involved in addictive behavior. Background: The current disorder concept of addiction includes neurobiological foundations and neurobiological research assuming irreversible molecular and structural changes within the brain dopamine reinforcement system, constituting the 'molecular and structural switch' from controlled drug intake to compulsive drug abuse. However, those irreversible changes have not so far been identified and it is suggested that in addition to the mesolimbic dopamine system, other brain systems including the mesocortical and nigrostriatal pathways as well as their non- dopaminergic feedback-loops might be involved in addictive behavior. Neurobiological approach: A three-step neurobiological approach is described that allows in a first step via novel animal models and imaging techniques to identify the neuroanatomical sites mediating voluntary drug intake, reinstatement of drug-seeking behavior, relapse, loss of control and drug intake despite negative consequences. In a subsequent step, forward genetic approaches including quantitative trait loci (QTL)-analysis and gene expression profiling are helpful in identifying so-called candidate genes. In a final step, conditional animal mutants and selective pharmacological tools are used to functionally validate candidate genes. Following this validation process, the transfer to the human situation has to be made and candidate genes have to be verified further in well-phenotyped cohorts of addicted patients. Conclusion: This three-step neurobiological approach, that must involve an interdisciplinary team including experimental psychologists, geneticists, molecular biologists and finally clinical addiction researchers, will allow us to understand where and how the addicted brain goes awry. copyright 2005 Society for the Study of Addiction. ISSN 0965-2140 Publication Type Journal: Article Journal Name Addiction Volume 100 Issue Part 12 Page 1813-1822 Year of Publication 2005 Date of Publication Dec 2005 NEURO (PHARM) <59> Database EMBASE Accession Number 2005529691 Authors Kalivas P.W. Institution (Kalivas) Department of Neurosciences, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29465, United States. Country of Publication United Kingdom Title New directions pharmacotherapy for addiction or can we forget to be addicted? Source Clinical Neuroscience Research. 5(2-4)(pp 147-150), 2005. Date of Publication: Nov 2005. Abstract Addiction is characterized by an uncontrollable drive to obtain drugs and reduced drive to seek biological rewards. These behavioral changes result from enduring neuroplasticity in brain circuits that underlie motivation and the initiation of adaptive behaviors. In most cases, the pharmacological treatments have been only modestly successful or failed to alter the cardinal features of addiction. However, recent advances in the neurobiology of synaptic plasticity, and in particular plasticity elicited in animal models of addiction, provide novel potential pharmacological targets for treating addicts. Since addiction results from pathological forms of neuroplasticity, it is proposed that targeting and normalizing these adaptations may more effectively ameliorate the behaviors that characterize addiction than current pharmacotherapies. copyright 2005 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved. ISSN 1566-2772 Publication Type Journal: Article Journal Name Clinical Neuroscience Research Volume 5 Issue Part 2-4 Page 147-150 Year of Publication 2005 Date of Publication Nov 2005

NEURO <60> Database EMBASE Accession Number 2005529690 Authors Saal D. Malenka R.C. Institution (Saal) Department of Psychiatry and Behavioral Science, Emory University, Atlanta, GA, United States. (Malenka) Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, United States. (Malenka) Stanford Medical Center, 1201 Welch Rd., Palo Alto, CA 94304-5485, United States. Country of Publication United Kingdom Title The role of synaptic plasticity in addiction. Source Clinical Neuroscience Research. 5(2-4)(pp 141-146), 2005. Date of Publication: Nov 2005. Abstract The activity-dependent modifications in neural circuits that underlie all forms of experience- dependent plasticity are thought to involve long-lasting changes in the strength of synaptic transmission at excitatory synapses. The most well characterized forms of such synaptic plasticity, termed long-term potentiation (LTP) and long-term depression (LTD), have been implicated in playing important roles in several forms of adaptive learning and memory. Here we review evidence that similar forms of synaptic plasticity in the mesolimbic dopamine system, specifically the ventral tegmental area (VTA) and nucleus accumbens (NAc), are elicited by drugs of abuse. These long-lasting drug-induced adaptations in key neural circuits may play important roles in the development and maintenance of addiction. copyright 2005 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved. ISSN 1566-2772 Publication Type Journal: Article Journal Name Clinical Neuroscience Research Volume 5 Issue Part 2-4 Page 141-146 Year of Publication 2005 Date of Publication Nov 2005

NEURO <63> Database EMBASE Accession Number 2005529686 Authors Koob G.F. Institution (Koob) Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States. Country of Publication United Kingdom Title The neurocircuitry of addiction: Implications for treatment. Source Clinical Neuroscience Research. 5(2-4)(pp 89-101), 2005. Date of Publication: Nov 2005. Abstract Drug addiction is a chronic, relapsing disorder characterized by a compulsion to seek and take drugs, loss of control in limiting intake, and emergence of a negative emotional state in the absence of drug. Allostatic changes in reward function that lead to excessive drug intake provide a heuristic framework to identify the neurobiological and neuroadaptive mechanisms involved in the development of drug addiction. The brain reward system implicated in the development of addiction is comprised of key elements of the extended amygdala basal forebrain macrostructure and its connections. Neuropharmacological studies in animal models of addiction associated with excessive drug intake have provided evidence for the dysregulation of specific neurochemical mechanisms within the extended amygdala (opioid peptides, gamma-aminobutyric acid, glutamate, and dopamine). There also is recruitment of brain stress systems (corticotropin-releasing factor and norepinephrine) and dysregulation of brain anti-stress systems (neuropeptide Y), contributing to the negative motivational state associated with drug abstinence. The changes in the reward and stress systems are hypothesized to maintain hedonic stability in an allostatic state-as opposed to a homeostatic state-and as such, convey the vulnerability for the development of dependence and relapse. The compromised brain reward and stress systems provide additional motivation for drug- seeking derived from the negative reinforcement of acute withdrawal, and are hypothesized to contribute to the allostatic state of protracted abstinence that augments other forms of 'craving' induced by environmental events. The allostatic state of protracted abstinence is an important target for developing novel behavioral and pharmacological therapies for drug addiction. copyright 2005 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved. ISSN 1566-2772 Publication Type Journal: Article Journal Name Clinical Neuroscience Research Volume 5 Issue Part 2-4 Page 89-101 Year of Publication 2005 Date of Publication Nov 2005

NEURO / OPIOIDS <64> Database EMBASE Accession Number 2005529684 Authors Berettimi W. Institution (Berettimi) University of Pennsylvania, School of Medicine, Center for Neurobiology and Behavior, 415 Curie Blvd., Philadelphia, PA 19104, United States. Country of Publication United Kingdom Title The human mu opioid receptor gene in addictions. Source Clinical Neuroscience Research. 5(2-4)(pp 69-73), 2005. Date of Publication: Nov 2005. Abstract This paper will review the evidence that the human mu opioid receptor gene influences risk for addictions. The structure of the gene will be delineated. Animal model work will be summarized briefly, indicating what drug addictions might be influenced by the mu opioid receptor gene. Finally, human genetic studies will be examined. copyright 2005 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved. ISSN 1566-2772 Publication Type Journal: Review Journal Name Clinical Neuroscience Research Volume 5 Issue Part 2-4 Page 69-73 Year of Publication 2005 Date of Publication Nov 2005

NEURO <65> Database EMBASE Accession Number 2005529516 Authors Panossian A. Wagner H. Institution (Panossian) Swedish Herbal Institute, Viktor Rydbergsgatan 10, SE-411 32, Gothenburg, Sweden. (Wagner) Centre of Pharma-Research, Pharmaceutical Biology, University of Munich, Butenandtstr. 5, D-81377 Munich, Germany. Country of Publication United Kingdom Title Stimulating effect of adaptogens: An overview with particular reference to their efficacy following single dose administration. Source Phytotherapy Research. 19(10)(pp 819-838), 2005. Date of Publication: Oct 2005. Abstract Plant adaptogens are compounds that increase the ability of an organism to adapt to environmental factors and to avoid damage from such factors. The beneficial effects of multi- dose administration of adaptogens are mainly associated with the hypothalamic-pituitary- adrenal (HPA) axis, a part of the stress-system that is believed to play a primary role in the reactions of the body to repeated stress and adaptation. In contrast, the single dose application of adaptogens is important in situations that require a rapid response to tension or to a stressful situation. In this case, the effects of the adaptogens are associated with another part of the stress-system, namely, the sympatho-adrenal-system (SAS), that provides a rapid response mechanism mainly to control the acute reaction of the organism to a stressor. This review focuses primarily on the SAS-mediated stimulating effects of single doses of adaptogens derived from Rhodiola rosea, Schizandra chinensis and Eleutherococcus senticosus. The use of these drugs typically generates no side effects, unlike traditional stimulants that possess addiction, tolerance and abuse potential, produce a negative effect on sleep structure, and cause rebound hypersomnolence or 'come down' effects. Furthermore, single administration of these adaptogens effectively increases mental performance and physical working capacity in humans. R. rosea is the most active of the three plant adaptogens producing, within 30 min of administration, a stimulating effect that continues for at least 4-6 h. The active principles of the three plants that exhibit single dose stimulating effects are glycosides of phenylpropane- and phenylethane-based phenolic compounds such as salidroside, rosavin, syringin and triandrin, the latter being the most active. Copyright copyright 2005 John Wiley & Sons, Ltd. ISSN 0951-418X Publication Type Journal: Review Journal Name Phytotherapy Research Volume 19 Issue Part 10 Page 819-838 Year of Publication 2005 Date of Publication Oct 2005

NEURO <66> Database EMBASE Accession Number 2005529379 Authors Bechara A. Van Der Linden M. Institution (Bechara) Division of Cognitive Neuroscience, Department of Neurology, University of Iowa College of Medicine, Iowa City, IA, United States. (Van Der Linden) Cognitive Psychopathology and Neuropsychology Unit, FPSE, University of Geneva, Geneva, Switzerland. (Bechara) Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, United States. Country of Publication United Kingdom Title Decision-making and impulse control after frontal lobe injuries. Source Current Opinion in Neurology. 18(6)(pp 734-739), 2005. Date of Publication: Dec 2005. Abstract Purpose of review: For a long time, the prefrontal cortex has been considered a 'nonfunctional' brain area, and understanding its function has lagged behind other areas. This is no longer true since appreciation of the vital role that this brain region plays in adaptive behaviors, and especially decision-making, is now evident more than ever. The present review highlights recent progress made in this area of research. Recent findings: Decision- making is a term often referred to in the psychological literature as one of the 'executive functions' that play a role in managing (like an executive) other cognitive functions, such as memory, attention, and language. Considerable research efforts have been directed towards differentiating various processes of executive functions, but much of this effort in the past has focused on the dorsolateral prefrontal cortex sector. Here we will review findings that address decision-making and its link to the ventromedial prefrontal cortex. Summary: Decision-making impairments as encountered in neurological and psychiatric patients are costly in terms of individual human suffering and in financial terms. In addition to its obvious value in advancing fundamental knowledge in neuroscience, understanding the neural mechanisms of decision- making is likely to have important practical consequences, including the understanding and management of neuropsychiatric disorders such as addiction, as well as the management of a considerable number of elderly people suffering from a decline in cognitive functions critical for decision-making, in spite of relatively intact memory and general intellect, which impact real-life matters that are important to themselves and their family. copyright 2005 Lippincott Williams & Wilkins. ISSN 1350-7540 Publication Type Journal: Review Journal Name Current Opinion in Neurology Volume 18 Issue Part 6 Page 734-739 Year of Publication 2005 Date of Publication Dec 2005

NEURO (PHARM) <70> Database EMBASE Accession Number 2005521201 Authors Thatte S. Datar K. Ottenbrite R.M. Institution (Thatte, Datar, Ottenbrite) Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23284, United States. Country of Publication United Kingdom Title Perspectives on: Polymeric drugs and drug delivery systems. Source Journal of Bioactive and Compatible Polymers. 20(6)(pp 585-601), 2005. Date of Publication: Nov 2005. Abstract Therapeutic uses of a variety of drug carrier systems have significant impact on the treatment and potential cure of many chronic diseases, including cancer, diabetes, mellitus, rheumatoid arthritis, HIV infection, and drug addiction. Drug delivery technology is a multidisciplinary science involving the physical, biological, medicinal, pharmaceutical, biomedical engineering and biomaterial fields. Polymeric systems can deliver drugs directly to the intended site of action and can also improve efficacy while minimizing unwanted side effects elsewhere in the body, which often limit the long-term use of many drugs. In this article, some recent publications on several polymeric drug conjugates, gene delivery systems and polymer implants are addressed. copyright 2005 SAGE Publications. ISSN 0883-9115 Publication Type Journal: Review Journal Name Journal of Bioactive and Compatible Polymers Volume 20 Issue Part 6 Page 585-601 Year of Publication 2005 Date of Publication Nov 2005

NEURO (? A) <83> Database EMBASE Accession Number 2005513670 Authors Harris G.C. Wimmer M. Aston-Jones G. Institution (Harris, Wimmer, Aston-Jones) Laboratory of Neuromodulation and Behavior, Department of Psychiatry, University of Pennsylvania, 705 S. Chance/6100 422 Curie Blvd, Philadelphia, PA 19104-6100, United States. Country of Publication United Kingdom Title A role for lateral hypothalamic orexin neurons in reward seeking. Source Nature. 437(7058)(pp 556-559), 2005. Date of Publication: 22 Sep 2005. Abstract The lateral hypothalamus is a brain region historically implicated in reward and motivation, but the identity of the neurotransmitters involved are unknown. The orexins (or hypocretins) are neuropeptides recently identified as neurotransmitters in lateral hypothalamus neurons. Although knockout and transgenic overexpression studies have implicated orexin neurons in arousal and sleep, these cells also project to reward-associated brain regions, including the nucleus accumbens and ventral tegmental area. This indicates a possible role for these neurons in reward function and motivation, consistent with previous studies implicating these neurons in feeding. Here we show that activation of lateral hypothalamus orexin neurons is strongly linked to preferences for cues associated with drug and food reward. In addition, we show that chemical activation of lateral hypothalamus orexin neurons reinstates an extinguished drug-seeking behaviour. This reinstatement effect was completely blocked by prior administration of an orexin A antagonist. Moreover, administration of the orexin A peptide directly into the ventral tegmental area also reinstated drug-seeking. These data reveal a new role for lateral hypothalamus orexin neurons in reward-seeking, drug relapse and addiction. copyright 2005 Nature Publishing Group. ISSN 0028-0836 Publication Type Journal: Article Journal Name Nature Volume 437 Issue Part 7058 Page 556-559 Year of Publication 2005 Date of Publication 22 Sep 2005

NEURO (A) <84> Database EMBASE Accession Number 2005512208 Authors Singh M.E. McGregor I.S. Mallet P.E. Institution (Singh, Mallet) School of Psychology, University of New England, Armidale, NSW 2351, Australia. (McGregor) School of Psychology, Sydney University, Sydney, NSW 2006, Australia. Country of Publication United Kingdom Title Repeated exposure to Delta⁹-tetrahydrocannabinol alters heroin-induced locomotor sensitisation and Fos-immunoreactivity. Source Neuropharmacology. 49(8)(pp 1189-1200), 2005. Date of Publication: Dec 2005. Abstract The present study examined the effect of chronic exposure to Delta⁹- tetrahydrocannabinol (THC) on heroin-induced locomotor sensitisation and Fos- immunoreactivity (Fos-IR). Adult male albino Wistar rats (n = 60) were injected intraperitoneally (i.p.) 21 times with vehicle, 0.05, 0.5, or 5.0 mg/kg THC (once every 48 h for 41 days). Locomotor activity was assessed for 180 min on pre-exposure days 1, 21, and 41. Following a 2-week washout period, rats were divided into five equal groups (n = 12) and injected subcutaneously (s.c.) with vehicle or heroin (0.5 mg/kg). Locomotor activity was recorded for 240 min. In drug-naive rats, heroin significantly increased locomotor activity. THC pre-exposure further increased heroin-induced locomotion. After an interval of 2 weeks, rats pre-exposed to vehicle and 5.0 mg/kg THC in the first part of the experiment were randomly assigned to one of four treatment groups (n = 6) and injected s.c. with vehicle or 0.5 mg/kg heroin and perfused 2 h later. Fos-IR was examined in several brain regions. Acute heroin increased Fos-IR in drug-naive rats in the caudate-putamen (CPu; central, medial and dorsomedial regions), nucleus accumbens (NAC; core and shell regions), bed nucleus of the stria terminalis (BNST), lateral septum, central nucleus of the amygdala (CEA), periaqueductal grey (PAG; dorsolateral, dorsomedial, and lateral), and the Edinger-Westphal nucleus. Pre-exposure to THC significantly increased heroin-induced Fos-IR in the dorsomedial CPu and the NAC (core). Conversely, THC pre-exposure reduced heroin- induced Fos-IR in the BNST, CEA, and the PAG (dorsolateral and lateral). The present study demonstrates that THC pre-exposure increases the locomotor stimulating effects of heroin and provides new evidence for the neural correlates that may underlie cannabinoid and opioid cross-sensitisation. copyright 2005 Elsevier Ltd. All rights reserved. ISSN 0028-3908 Publication Type Journal: Article Journal Name Neuropharmacology Volume 49 Issue Part 8 Page 1189-1200 Year of Publication 2005 Date of Publication Dec 2005

NEURO (A) <92> Database EMBASE Accession Number 2005494110 Authors Zhang L. Liu Y. Chen X. Institution (Zhang, Liu, Chen) Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Nfld. A1B 3V6, Canada. (Chen) Discipline of Psychiatry Division, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Nfld. A1B 3V6, Canada. Country of Publication United Kingdom Title Carbachol induces burst firing of dopamine cells in the ventral tegmental area by promoting calcium entry through L-type channels in the rat. Source Journal of Physiology. 568(2)(pp 469-481), 2005. Date of Publication: 15 Oct 2005. Abstract Enhanced activity of the central dopamine system has been implicated in many psychiatric disorders including schizophrenia and addiction. Besides terminal mechanisms that boost dopamine levels at the synapse, the cell body of dopamine cells enhances terminal dopamine concentration through encoding action potentials in bursts. This paper presents evidence that burst firing of dopamine cells in the ventral tegmental area was under cholinergic control using nystatin-perforated patch clamp recording from slice preparations. The non-selective cholinergic agonist carbachol excited the majority of recorded neurones, an action that was not affected by blocking glutamate and GABA ionotropic receptors. Twenty per cent of dopamine cells responded to carbachol with robust bursting, an effect mediated by both muscarinic and nicotinic cholinoceptors postsynaptically. Burst firing induced as such was completely dependent on calcium entry as it could be blocked by cadmium and more specifically the L-type blocker nifedipine. In the presence of the sodium channel blocker tetrodotoxin, carbachol induced membrane potential oscillation that had similar kinetics and frequency as burst firing cycles and could also be blocked by cadmium and nifedipine. Direct activation of the L-type channel with Bay K8644 induced strong bursting which could be blocked by nifedipine but not by depleting internal calcium stores. These results indicate that carbachol increases calcium entry into the postsynaptic cell through L-type channels to generate calcium-dependent membrane potential oscillation and burst firing. This could establish the L-type channel as a target for modulating the function of the central dopamine system in disease conditions. copyright The Physiological Society 2005. ISSN 0022-3751 Publication Type Journal: Article Journal Name Journal of Physiology Volume 568 Issue Part 2 Page 469-481 Year of Publication 2005 Date of Publication 15 Oct 2005

NEURO <105> Database EMBASE Accession Number 2005470805 Authors Joranby L. Pineda K.F. Gold M.S. Institution (Joranby, Pineda, Gold) University of Florida, College of Medicine, P.O. Box 10183, Gainesville, FL 32610, United States. Country of Publication United Kingdom Title Addiction to food and brain reward systems. Source Sexual Addiction and Compulsivity. 12(2-3)(pp 201-217), 2005. Date of Publication: 2005. Abstract Overeating is emerging as one of the most pressing health issues affecting developed countries. While it is known that overeating leads to overweight and obesity and a number of associated health risks, the etiology of overeating remains unclear. Overeating shares many characteristics with substance use disorders. Furthermore, overeating has been characterized as an addiction and most likely arises from a combination of abnormal cognitive and neuroendocrine processes. Although emotional states have been shown to mediate reward processing, the implications for hunger mediating reward have not been fully elucidated. In this paper, we discuss the relationship between overeating and obesity with other substance addictions and the neural circuitry they share. Additionally, we discuss genetic and environmental influences on eating behaviors and the implications that these influences have on treatment. Copyright copyright Taylor & Francis, Inc. ISSN 1072-0162 Publication Type Journal: Article Journal Name Sexual Addiction and Compulsivity Volume 12 Issue Part 2-3 Page 201-217 Year of Publication 2005 Date of Publication 2005

NEURO <106> Database EMBASE Accession Number 2005470802 Authors Schmitz J.M. Institution (Schmitz) Two Rivers Psychiatric Hospital, Kansas City, MO, United States. (Schmitz) 1124 West Main Street, Blue Springs, MO 64015, United States. Country of Publication United Kingdom Title The interface between impulse-control disorders and addictions: Are pleasure pathway responses shared neurobiological substrates? Source Sexual Addiction and Compulsivity. 12(2-3)(pp 149-168), 2005. Date of Publication: 2005. Abstract The term "addiction" has been used to describe several Impulse-Control Disorders. Models that have been developed for Substance Related Disorders suggest a more general applicability in understanding and treating Impulse-Control Disorders. Neurocircuits and the neurochemical mediation of pleasure responses may represent a shared neurobiological substrate, linking addictions of both types. In this review, Pathological Gambling, Kleptomania, Compulsive Buying, Pyromania, and Problematic Internet Use are examined from a neurobiological perspective, with a specific focus on pleasure pathway responses. Copyright copyright Taylor & Francis, Inc. ISSN 1072-0162 Publication Type Journal: Review Journal Name Sexual Addiction and Compulsivity Volume 12 Issue Part 2-3 Page 149-168 Year of Publication 2005 Date of Publication 2005

NEURO <107> Database EMBASE Accession Number 2005470801 Authors Schneider J.P. Sealy J. Montgomery J. Irons R.R. Institution (Schneider) Arizona Community Physicians, Tucson, AZ, United States. (Sealy) Del Amo Hospital, Torrance, CA, United States. (Irons) Menninger Clinic, Topeka, KS, United States. (Schneider) 1500 N. Wilmott, Tucson, AZ 85712, United States. Country of Publication United Kingdom Title Ritualization and reinforcement: Keys to understanding mixed addiction involving sex and drugs. Source Sexual Addiction and Compulsivity. 12(2-3)(pp 121-148), 2005. Date of Publication: 2005. Abstract Treatment of patients with multiple addictions begins with assessment in various areas, including the patient's particular addiction interaction pattern, and the effect of the addictions on his or her life and relationships. Some questions to consider in the first category include: Are the addictions alternating or are they parallel? Do they interact in an escalating fashion? Two common ways in which multiple addictions interact are ritualization and reinforcement. This paper describes the nature of ritualization and how rituals reinforce maintenance of an addictive cycle that include both sex and drugs. We describe the ways this process is played out in three scenarios: (1) Addicts who isolate as the paramount feature of a particular ritualized pattern of sex and drugs; (2) women who try to manage childhood trauma and domestic violence through addictive rituals; and (3) gay addicts who use ongoing multiple partners as a ritual to maintain intensity. We also present suggestions for clinicians working with these three populations. Copyright copyright Taylor & Francis, Inc. ISSN 1072-0162 Publication Type Journal: Article Journal Name Sexual Addiction and Compulsivity Volume 12 Issue Part 2-3 Page 121-148 Year of Publication 2005 Date of Publication 2005

NEURO (PHARM) <109> Database EMBASE Accession Number 2005470339 Authors Mucke H.A.M. Institution (Mucke) HM Pharma Consultancy, Enenkelstrasse 28/32, A-1160 Wien, Austria. Country of Publication United Kingdom Title The European Association of Addiction Therapy - Inaugural Conference. 6-8 July 2005, Budapest, Hungary. Source IDrugs. 8(10)(pp 816-817), 2005. Date of Publication: Oct 2005. Abstract While it is true that the drug developers found far fewer presentations of immediate interest than, did the practitioners from hospitals and community services dedicated to addiction therapy, the first EAAT meeting provided an excellent cross-sectional snapshot of the environment and patient profiles that developers of addiction pharmacotherapies need to take into account. This would be an important integrative achievement in a therapeutic field that has not experienced much pharmacological innovation, and which, in spite of its small size, is highly fragmented. copyright The Thomson Corporation. ISSN 1369-7056 Publication Type Journal: Conference Paper Journal Name IDrugs Volume 8 Issue Part 10 Page 816-817 Year of Publication 2005 Date of Publication Oct 2005

NEURO (A) <110> Database EMBASE Accession Number 2005463665 Authors Holmes A. Le Guisquet A.M. Vogel E. Millstein R.A. Leman S. Belzung C. Institution (Holmes, Millstein) Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-1256, United States. (Holmes, Millstein) 5625 Fishers Lane, 2N09, Rockville, MD 20852, United States. (Le Guisquet, Vogel, Leman, Belzung) EA3248 Psychobiologie des Emotions, UFR Sciences et Techniques, Parc Grandmont, F-37200 Tours, France. Country of Publication United Kingdom Title Early life genetic, epigenetic and environmental factors shaping emotionality in rodents. Source Neuroscience and Biobehavioral Reviews. 29(8)(pp 1335-1346), 2005. Date of Publication: 2005. Abstract Childhood trauma is known to increase risk for emotional disorders and addiction. However, little is currently understood about the neurodevelopmental basis of these effects, or how genetic and epigenetic factors interact with the environment to shape the systems subserving emotionality. In this review, we discuss the use of rodent models of early life emotional experience to study these issues in the laboratory and present some of our pertinent findings. In rats, postnatal maternal separation can produce lasting increases in emotional behavior and stressor-reactivity, together with alterations in various brain neurotransmitter systems implicated in emotionality, including corticotropin-releasing factor, serotonin, norepinephrine, and glutamate. Genetic differences between inbred mouse strains have been exploited to further study how maternal behavior affects emotional development using techniques such as cross-fostering and generation of inter-strain hybrids. Together with our own recent data, the findings of these studies demonstrate the pervasive influence of maternal and social environments during sensitive developmental periods and reveal how genetic factors determine how these early life experiences can shape brain and behavior throughout life. copyright 2005 Elsevier Ltd. All rights reserved. ISSN 0149-7634 Publication Type Journal: Conference Paper Journal Name Neuroscience and Biobehavioral Reviews Volume 29 Issue Part 8 Page 1335-1346 Year of Publication 2005 Date of Publication 2005

NEURO (GENETICS) <122> Database EMBASE Accession Number 2005461708 Authors Luciano M. Kirk K.M. Heath A.C. Martin N.G. Institution (Luciano, Kirk, Martin) Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, Australia. (Heath) Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States. (Luciano) Queensland Institute of Medical Research, Herston, QLD 4029, Australia. Country of Publication United Kingdom Title The genetics of tea and coffee drinking and preference for source of caffeine in a large community sample of Australian twins. Source Addiction. 100(10)(pp 1510-1517), 2005. Date of Publication: Oct 2005. Abstract Aims: To investigate the genetic and environmental influences on tea consumption and their commonalities with coffee consumption; and to further examine the genetic and environmental aetiology of preference for tea/coffee. Design: A classical twin design was used in which the similarity of identical and non-identical twins is compared, enabling estimates of genetic, common environmental and unique environmental influence on the trait. Setting and participants: An Australian population-based sample of 1796 identical (i.e. monozygotic) and 2013 non-identical (i.e. dizygotic) twin pairs aged 16-87 years was studied, roughly three-fifths of whom were female. The sample represented approximately 70% of those approached for study participation. Measurements: As part of a Health and Lifestyle Questionnaire, respondents were asked how many cups of each tea and coffee they consumed per day. Additional measures of 'total tea and coffee consumption' and 'preference for coffee' were calculated. Findings: Age was positively associated with tea consumption but negatively associated with coffee preference; women consumed more beverages than men, but showed a lower preference for coffee. An inverse relation between tea and coffee consumption-larger in females (-0.41) than males (-0.34)-was supported. This association was mediated entirely by the unique environment in males, and by both the unique environment (68.3%) and genes (31.7%) in females. Tea and coffee drinking were shown to have similar heritabilities (0.46) in males, but tea consumption was influenced by common environmental factors whereas coffee consumption was not. Coffee preference was shown to be influenced by genes (0.42) and the unique environment (0.58). Conclusions: As the patterns of genetic and environmental variation were shown to differ for tea and coffee consumption it may be more informative to retain them as separate measures of caffeine intake in future studies of stimulant use and taste perception. copyright 2005 Society for the Study of Addiction. ISSN 0965-2140 Publication Type Journal: Article Journal Name Addiction Volume 100 Issue Part 10 Page 1510-1517 Year of Publication 2005 Date of Publication Oct 2005

NEURO (GENETICS) <133> Database EMBASE Accession Number 2005460324 Authors Saxon A.J. Oreskovich M.R. Brkanac Z. Institution (Saxon, Brkanac) Department of Psychiatry, University of Washington School of Medicine, (Saxon, Brkanac) Center of Excellence in Substance Abuse Treatment and Education, Mental Illness Research Educational and Clinical Center, VA Puget Sound Health Care System, (Oreskovich) Washington Physicians Health Plan, Seattle, WA, United States. (Saxon) Department of Psychiatry and Behavioral Sciences, University of Washington, School of Medicine, 1660 S. Columbian Way, Seattle, WA 98108, United States. Country of Publication United Kingdom Title Genetic determinants of addiction to opioids and cocaine. Source Harvard Review of Psychiatry. 13(4)(pp 218-232), 2005. Date of Publication: Jul 2005. Abstract Objective: The completion of the human genome sequence has spurred investigation of the genetic contribution to substance dependence. In this article some of the recent scientific evidence for genetic determinants of opioid and cocaine dependence is reviewed. Method: An electronic search of the medical literature was conducted to locate published studies relevant to the genetics of opioid and cocaine dependence. The collected information judged to be most pertinent is described and discussed. Results: Genetic epidemiologic studies support a high degree of heritable vulnerability for both opioid and cocaine dependence. Polymorphisms in the genes coding for dopamine receptors and transporter, opioid receptors, endogenous opioid peptides, cannabinoid receptors, and serotonin receptors and transporter all appear to be associated with the phenotypic expression of this vulnerability once opioids or cocaine are consumed. Conclusions: Despite this initial progress, identification of specific genes and quantification of associated risk for the expression of each gene remain to be elucidated. While alteration of an individual's genome to change the phenotype seems remote, future interventions for treatment of opioid and cocaine dependence may include precise medications targeted to block the effects of proteins that have been identified through genetic research. copyright 2005 President and Fellows of Harvard College. ISSN 1067-3229 Publication Type Journal: Review Journal Name Harvard Review of Psychiatry Volume 13 Issue Part 4 Page 218-232 Year of Publication 2005 Date of Publication Jul 2005

NEURO (GENETICS) <148> Database EMBASE Accession Number 2005446239 Authors Rothstein M.A. Institution (Rothstein) Institute for Bioethics, Health Policy and Law, University of Louisville, School of Medicine, 501 East Broadway #310, Louisville, KY 40202, United States. Country of Publication United Kingdom Title Applications of behavioural genetics: Outpacing the science? Source Nature Reviews Genetics. 6(10)(pp 793-798), 2005. Date of Publication: Oct 2005. Abstract Human behavioural genetics is an established research discipline of the genomic age, and applications for behavioural genetic information are most likely to emerge in areas such as criminal justice, education, employment and insurance. However, behavioural genetic research into personality traits and antisocial behaviour poses several risks; for example, tentative or preliminary research findings might be misused in legal and commercial settings. Scientific caution, public and media education, expert consultation and confidentiality protection are essential for the responsible use of behavioural genetics. copyright 2005 Nature Publishing Group. ISSN 1471-0056 Publication Type Journal: Review Journal Name Nature Reviews Genetics Volume 6 Issue Part 10 Page 793-798 Year of Publication 2005 Date of Publication Oct 2005

CANNABIS <149> Database EMBASE Accession Number 2005445274 Authors Menghrajani P. Klaue K. Dubois-Arber F. Michaud P.-A. Institution (Menghrajani, Klaue, Michaud) Research Group on Adolescent Health, University Institute for Social and Preventive Medicine, CHUV, 1011 Lausanne, Switzerland. (Dubois-Arber) Unit for the Evaluation of Preventive Programs, University Institute for Social and Preventive Medicine, CHUV, 1011 Lausanne, Switzerland. Country of Publication United Kingdom Title Swiss adolescents' and adults' perceptions of cannabis use: A qualitative study. Source Health Education Research. 20(4)(pp 476-484), 2005. Date of Publication: Aug 2005. Abstract Few studies have attempted to investigate the nature of adolescents' and adults' conceptions and perceptions of cannabis use. Our objectives were to explore adolescent and adult perception of use and misuse of cannabis, and their opinions and beliefs about the current legal context and preventive strategies. We used focus group discussions with four categories of stakeholders: younger (12-15 year old) adolescents, older (16-19 year old) adolescents, parents of teenagers and professionals working with young people. In some areas (legal framework, role of the media, importance of early preventive interventions), we found consensual attitudes and beliefs across the four groups of participants. In all four groups, participants did not have any consensual vision of the risks of cannabis use or the definition of misuse. In the area of the prevention of cannabis use/misuse, while parents focused on the potential role of professionals and the media, thus minimizing their own educational and preventive role, professionals stressed the importance of parental control and education. Within the Swiss context, we conclude there exists an urgent need for information and clarification of the issues linked with cannabis use and misuse directed at parents and professionals. copyright Oxford University Press 2004; All rights reserved. ISSN 0268-1153 Publication Type Journal: Article Journal Name Health Education Research Volume 20 Issue Part 4 Page 476-484 Year of Publication 2005 Date of Publication Aug 2005

NEURO (A) <163> Database EMBASE Accession Number 2005418290 Authors Andrzejewski M.E. Spencer R.C. Kelley A.E. Institution (Andrzejewski, Spencer, Kelley) Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Boulevard, Madison, WI 53719, United States. (Kelley) Neuroscience Training Program, University of Wisconsin-Madison, 6001 Research Park Boulevard, Madison, WI 53719, United States. Country of Publication United Kingdom Title Instrumental learning, but not performance, requires dopamine D1-receptor activation in the amygdala. Source Neuroscience. 135(2)(pp 335-345), 2005. Date of Publication: 2005. Abstract Substantial experimental evidence exists suggesting a critical role for dopamine in reinforcer-related processes, such as learning and drug addiction. Dopamine receptors, and in particular D1 receptors, are widely considered as modulators of synaptic plasticity. The amygdala contains both dopamine terminals and dopamine D1 receptors and is intimately involved in motivation and learning. However, little is known about the involvement of D1 receptor activation in two subnuclei of the mammalian amygdala, the central nucleus and basolateral complex in instrumental learning. Following recovery from surgery and preliminary training, rats with bilateral indwelling cannulae aimed at the central nucleus or basolateral complex were trained to lever-press for sucrose pellets over 12 sessions. Infusion of the selective D1 antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine hydrochloride (0.3nmol and 3.0nmol) prior to the first five training sessions dose- dependently impaired instrumental learning when compared with vehicle-infused controls. All rats were then exposed to five sessions drug-free; lever-pressing quickly reached equal levels across groups. A drug infusion prior to an 11th session revealed no effect on performance. Control experiments indicated that basic motivational processes and general motor responses were intact, such as spontaneous feeding and locomotor activity. These results show an essential role for D1-receptor activation in both the central nucleus and basolateral complex on the acquisition of lever pressing for sucrose pellets in rats, but not the performance of the behavior once conditioned. We propose that instrumental learning is dependent on plasticity in the central nucleus and basolateral complex amygdala, and that D1 receptor activation participates in transcriptional processes that underlie this plasticity. copyright 2005 Published by Elsevier Ltd on behalf of IBRO. ISSN 0306-4522 Publication Type Journal: Article Journal Name Neuroscience Volume 135 Issue Part 2 Page 335-345 Year of Publication 2005 Date of Publication 2005

NEURO (GENETICS) <170> Database EMBASE Accession Number 2005416496 Authors Mannelli P. Patkar A.A. Murray H.W. Certa K. Peindl K. Mattila-Evenden M. Berrettini W.H. Institution (Mannelli, Patkar, Peindl, Mattila-Evenden) Department of Psychiatry, Duke University Medical Center, Durham, NC, United States. (Murray, Certa) Department of Psychiatry, Thomas Jefferson University, Philadelphia, PA, United States. (Berrettini) Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States. (Patkar) Department of Psychiatry, Duke University Medical Center, 4323 Ben Franklin Blvd, Durham, NC 27704, United States. Country of Publication United Kingdom Title Polymorphism in the serotonin transporter gene and response to treatment in African American cocaine and alcohol-abusing individuals. Source Addiction Biology. 10(3)(pp 261-268), 2005. Date of Publication: Sep 2005. Abstract The serotonin transporter (5-HTT) regulates serotonin transmission and modulates behavioral effects of drug of abuse. A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) yielding a short (S) and long (L) allele has been associated with severity of substance abuse. The aims of the study were to investigate whether 5-HTTLPR genotypes differed in their response to treatment in cocaine- and alcohol-abusing patients. Polymerase chain reaction-based genotyping of a 44 base pair insertion/deletion polymorphism was performed in 141 African American cocaine-dependent patients with concurrent alcohol use who were entering a 12-week behaviorally oriented outpatient treatment program. In treatment, end of treatment and 6-month follow-up outcome measures included changes in Addiction Severity Index (ASI) scores, urine drug screens, days in treatment, individual/group sessions, dropout and completion rates. As expected, there was a reduction in substance abuse by the end of treatment and follow-up (F = 5.15, p = 0.000). However, there were no differences in the reduction in cocaine use across the LL, LS and SS genotypes. Interestingly, individuals with the S allele showed greater severity of alcohol use at admission (F = 4.84, p = 0.03), and the SS genotype showed less improvement in alcohol measures than the LL at follow-up (F = 3.68, p = 0.03), after controlling for baseline variables. While we found no association of the 5-HTTLPR variants with severity of cocaine abuse or any cocaine-related outcome measures, the data suggested that the 5-HTTLPR polymorphism may distinguish responders from non-responders to behavioral treatment in terms of alcohol use. Further investigations are required to determine the role of the 5- HTTLPR polymorphism in influencing treatment - outcome among substance abusers. copyright Society for the Study of Addiction to Alcohol and Other Drugs. ISSN 1355-6215 Publication Type Journal: Article Journal Name Addiction Biology Volume 10 Issue Part 3 Page 261-268 Year of Publication 2005 Date of Publication Sep 2005

NEURO <175> Database EMBASE Accession Number 2005416302 Authors Dom G. Sabbe B. Hulstijn W. Van Den Brink W. Institution (Dom) Psychiatric Centre Brothers Alexians, Boechout, Belgium. (Sabbe) Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Belgium. (Hulstijn) Nijmegen Institute for Cognition and Information, Nijmegen, Netherlands. (Hulstijn) CAPRI, University of Antwerp, Belgium. (Van Den Brink) Department of Psychiatry, University of Amsterdam, Amsterdam Institute for Addiction Research (AIAR), Amsterdam, Netherlands. (Dom) Psychiatric Centre Brothers Alexians, Provinciesteenweg 408, 2530 Boechout, Belgium. Country of Publication United Kingdom Title Substance use disorders and the orbitofrontal cortex: Systematic review of behavioural decision-making and neuroimaging studies. Source British Journal of Psychiatry. 187(SEPT.)(pp 209-220), 2005. Date of Publication: Sep 2005. Abstract Background: Orbitofrontal cortex dysfunctions have been frequently documented in people with substance use disorders. The exact role of this cortical region, however, remains unspecified. Aims: To assess the functionality of the orbitofrontal cortex in people with substance use disorders. Method: Reports of studies using behavioural decision-making tasks and/or neuroimaging techniques to investigate orbitofrontal cortex functioning in cases of substance misuse were reviewed. Studies focusing exclusively on tobacco-smoking and gambling were excluded. Results: Fifty-two research articles were evaluated. Most studies showed significant deficits in decision-making in people with substance use disorders. A consistent finding in the neuroimaging studies was hypoactivity of the orbitofrontal cortex after detoxification. The association between hyperactivity of this region and craving or cue reactivity was not consistent across studies. Conclusions: The orbitofrontal cortex has an important role in addictive behaviours. Further studies are needed to elucidate the underlying neuronal substrates of cue reactivity, craving and decision-making, and the implications for treatment and relapse prevention. ISSN 0007-1250 Publication Type Journal: Review Journal Name British Journal of Psychiatry Volume 187 Issue Part SEPT. Page 209-220 Year of Publication 2005 Date of Publication Sep 2005

NEURO <193> Database EMBASE Accession Number 2005396165 Authors Hassoun Y. Razi K. Malhotra A.K. Institution (Hassoun, Razi, Malhotra) Department of Psychiatry Research, Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, NY, United States. (Malhotra) Department of Psychiatry Research, Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, 75-59 263rd Street, Glen Oaks, NY 11004, United States. Country of Publication United Kingdom Title The Third Annual Pharmacogenetics in Psychiatry Meeting, 2004. Source Psychiatric Genetics. 15(3)(pp 155-156), 2005. Date of Publication: Sep 2005. Abstract The Third Annual Pharmacogenetics In Psychiatry Meeting was held on 16th and 17th April 2004, in New York City, to discuss new developments and findings made in the area. This 2- day meeting was organized into five oral presentation sessions and one poster session. copyright 2005 Lippincott Williams & Wilkins. ISSN 0955-8829 Publication Type Journal: Conference Paper Journal Name Psychiatric Genetics Volume 15 Issue Part 3 Page 155-156 Year of Publication 2005 Date of Publication Sep 2005

NEURO (GENETICS) (A) <198> Database EMBASE Accession Number 2005388861 Authors Uz T. Ahmed R. Akhisaroglu M. Kurtuncu M. Imbesi M. Dirim Arslan A. Manev H. Institution (Uz, Ahmed, Akhisaroglu, Kurtuncu, Imbesi, Dirim Arslan, Manev) Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, Chicago, IL 60612, United States. Country of Publication United Kingdom Title Effect of fluoxetine and cocaine on the expression of clock genes in the mouse hippocampus and striatum. Source Neuroscience. 134(4)(pp 1309-1316), 2005. Date of Publication: 2005. Abstract Long-term drug-induced alterations in CNS gene expression may be responsible for some therapeutic effects, such as antidepressant action, as well as for psychopathological conditions, such as drug addiction and abuse. Transcription factors called "clock" genes can be affected by psychotropic drugs and may modify the expression pattern of other genes. In this study in mice, we investigated the delayed effects of single and repeated (i.e. 14 days) administration of the antidepressant fluoxetine and the psychostimulant cocaine on the brain expression of clock genes Period1, Period2, Period3, Clock, Bmal1, Cryptochrome1, Cryptochrome2, and NPAS2 (neuronal PAS domain protein 2), and their putative target gene, serotonin N-acetyltransferase. Mice were treated at ZT05 (lights on at 5:00 am; ZT00). Brain samples (i.e. hippocampus, striatum, and prefrontal cortex) were processed for a semi- quantitative mRNA assay. Repeated but not single treatment with either drug increased serotonin N-acetyltransferase expression in all areas tested. On the other hand, the expression of clock genes was differentially affected depending on the drug (i.e. fluoxetine and cocaine), treatment schedule (i.e. single and repeated), and brain area (i.e. hippocampus and striatum) tested. More pronounced changes were induced by repeated rather than single administrations of fluoxetine or cocaine. We propose that the effects of psychoactive drugs on clock transcription factors may mediate long-term drug-induced changes, possibly by regulating the expression of a second set of genes (i.e. clock-controlled genes). copyright 2005 Published by Elsevier Ltd on behalf of IBRO. ISSN 0306-4522 Publication Type Journal: Article Journal Name Neuroscience Volume 134 Issue Part 4 Page 1309-1316 Year of Publication 2005 Date of Publication 2005

NEURO (A) <204> Database EMBASE Accession Number 2005377625 Authors Le Foll B. Goldberg S.R. Sokoloff P. Institution (Le Foll, Goldberg) National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224, United States. (Sokoloff) Unite de Neurobiologie et Pharmacologie Moleculaire (INSERM U.573), Centre Paul Broca, 75014 Paris, France. Country of Publication United Kingdom Title The dopamine D₃ receptor and drug dependence: Effects on reward or beyond? Source Neuropharmacology. 49(4)(pp 525-541), 2005. Date of Publication: Sep 2005. Abstract Abused drugs (alcohol, heroin, cocaine, tetrahydrocannabinol and nicotine) elicit a variety of chronically relapsing disorders by interacting with brain reward systems. All of these drugs increase dopamine levels in the shell of nucleus accumbens, a structure that has been involved in their hedonic and reinforcing properties. Dopamine D₃ receptors (DRD3) are predominantly expressed in the nucleus accumbens, but also in the ventral tegmental area and in the amygdala, brain structures implicated in drug dependence. Moreover, converging pharmacological, human post-mortem and genetic studies have suggested the involvement of the DRD3 in drug dependence. Based on early studies using non-selective DRD3 ligands, the DRD3 was proposed as having a direct role in the rewarding effects of psychostimulants. However, recent studies using highly selective DRD3 ligands and the DRD3-deficient mice have revealed that the DRD3 is not implicated in the direct reinforcing effects of drugs of abuse. In contrast, the DRD3 appears to be implicated in the motivation to self-administer drugs under schedules where the response requirements are high. This is consistent with a behavioral economic analysis, with the effects of DRD3 ligands revealed only in situations with high prices for drug. Drug-self administration and relapse are strongly controlled by environmental stimuli. The DRD3 strongly modulates the influence of these environmental stimuli on drug-seeking behavior. DRD3 blockade disrupts the reactivity to drug-associated stimuli in various paradigms, such as second-order schedules of drug-self administration, conditioned place preference and Pavlovian conditioning procedures. In several paradigms, the involvement of the DRD3 has been confirmed by using DRD3- deficient mice. On the contrary, reactivity to stimuli associated with natural reinforcers, such as food, appears unaffected by modulation of the DRD3. All these findings suggest that DRD3 ligands may represent a useful strategy for decreasing relapse in abstinent drug-abusers. copyright 2005 Elsevier Ltd. All rights reserved. ISSN 0028-3908 Publication Type Journal: Review Journal Name Neuropharmacology Volume 49 Issue Part 4 Page 525-541 Year of Publication 2005 Date of Publication Sep 2005

NEURO <222> Database EMBASE Accession Number 2005353186 Authors Korutla L. Wang P.J. Mackler S.A. Institution (Korutla, Wang, Mackler) Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA, United States. (Mackler) Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States. (Mackler) Philadelphia Veterans Administration Medical Center (VAMC), Philadelphia, PA, United States. (Mackler) Department of Pharmacology, 067 John Morgan Building, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, Philadelphia, PA 19104, United States. Country of Publication United Kingdom Title The POZ/BTB protein NAC1 interacts with two different histone deacetylases in neuronal-like cultures. Source Journal of Neurochemistry. 94(3)(pp 786-793), 2005. Date of Publication: Aug 2005. Abstract NAC1 is a cocaine-regulated POZ/BTB (Pox virus and Zinc finger/Bric-a-brac Tramtrack Broad complex) protein. NAC1 is increased by cocaine selectively in the nucleus accumbens, a CNS region important for drug addiction. NAC1's role in the cell, however, is not known. Each of the two NAC1 isoforms, sNAC1 (short NAC1) and INAC1 (long NAC1), may serve as corepressors for other POZ/BTB proteins. This study investigated whether sNAC1 and INAC1 demonstrated protein-protein interactions with other corepressors. Histone deacetylase (HDAC) inhibition reversed sNAC1 and INAC1 repression of Gal4 luciferase, but only in neuronal-like cultures. Because these inhibitors do not distinguish among histone deacetylases, two histone deacetylases were selected for further study. HDAC 3 and 4 both demonstrated protein-protein interactions with sNAC1 and INAC1. This was shown using coimmunoprecipitations, glutathione-S-transferase (GST) pulldowns and mammalian two- hybrids. Importantly, either the POZ domain or NAC1 without the POZ domain can bind these two HDACs. Other corepressors, specifically NCoR (nuclear receptor corepressor), SMRT (silencing mediator for retinoid and thyroid hormone receptor) and mSin3a, do not exhibit protein-protein interactions with sNAC1 and INAC1. None showed protein-protein interactions in GST pulldowns or mammalian two-hybrids. Taken together, the results of these experiments indicate sNAC1 and INAC1 recruit histone deacetylases for transcriptional repression, further enhancing POZ/BTB protein mediated repression. copyright 2005 International Society for Neurochemistry. ISSN 0022-3042 Publication Type Journal: Article Journal Name Journal of Neurochemistry Volume 94 Issue Part 3 Page 786-793 Year of Publication 2005 Date of Publication Aug 2005

NEURO <227> Database EMBASE Accession Number 2005340600 Authors Ramage S.N. Anthony I.C. Carnie F.W. Busuttil A. Robertson R. Bell J.E. Institution (Ramage, Anthony, Carnie, Bell) Neuropathology Unit, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom. (Busuttil) Forensic Medicine Unit, University of Edinburgh, Edinburgh, United Kingdom. (Robertson) Muirhouse Medical Centre, Muirhouse Avenue, Edinburgh, United Kingdom. (Bell) Department of Pathology (Neuropathology), University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom. Country of Publication United Kingdom Title Hyperphosphorylated tau and amyloid precursor protein deposition is increased in the brains of young drug abusers. Source Neuropathology and Applied Neurobiology. 31(4)(pp 439-448), 2005. Date of Publication: Aug 2005. Abstract Drug abuse is a major problem worldwide. The incidence of drug-related deaths attributed to opiate abuse is increasing annually. Apart from routine examination, little is known of the neuropathology of drug abuse. We, and others, have shown previously that drug abuse is associated with microglial activation. We hypothesised that neuroinflammation might lead to premature neurodegeneration in drug abusers. We investigated the brains of young opiate abusers (n = 34, all < 40 years) for the presence of proteins associated with neurodegenerative diseases and compared them with the brains of age-matched, non-drug users (n = 16) all of whom died suddenly. Detailed immunohistochemical analysis of the hippocampus, brainstem and basal ganglia for hyperphosphorylated tau, beta-amyloid, beta- amyloid precursor protein (betaAPP) and ubiquitin demonstrated an excess of AT8-positive neurofibrillary tangles (NFT) in the drug abusers. These were not only more prevalent in the drug abusers than in controls (44% vs. 19%) but also involved more brain areas. In controls NFT were confined to the entorhinal cortex whereas in drug users they were also found in the subiculum, temporal neocortex, nucleus basalis of Meynert and the locus coeruleus. Virtually no amyloid plaques were present but betaAPP positivity was again much more common in drug abusers than controls (73% vs. 20% in the brainstem and 59% vs. 23% in the temporal lobe). There is no suggestion that these drug abusers had displayed major cognitive impairment although detailed neuropsychological assessment is difficult in this subject group. Likely causes of hyperphosphorylated tau deposition in drug abuse include hypoxic-ischaemic injury, microglial-associated cytokine release and possibly drug-associated neurotoxicity or hepatitis. Head injury which is another major risk factor, does not appear to have contributed to our findings. Genetic factors also merit consideration. It is unclear at present how much of the hyperphosphorylated tau detected in these young drug abusers represents a transitory phenomenon. copyright 2005 Blackwell Publishing Ltd. ISSN 0305-1846 Publication Type Journal: Article Journal Name Neuropathology and Applied Neurobiology Volume 31 Issue Part 4 Page 439-448 Year of Publication 2005 Date of Publication Aug 2005

NEURO <230> Database EMBASE Accession Number 2005330034 Authors Chen T.J.H. Blum K. Mathews D. Fisher L. Schnautz N. Braverman E.R. Schoolfield J. Downs B.W. Comings D.E. Institution (Chen) Chang Jung Christian University, Taiwan, Province of China. (Chen) Changhua Christian Hospital, Changhua, Taiwan, Province of China. (Blum) Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, United States. (Blum) PharmacoGenomics, Inc., San Antonio, TX, United States. (Blum) SaluGen, Inc., San Diego, CA, United States. (Mathews, Fisher) Comprehensive Neurobehavioral Systems, Cedar Park, TX, United States. (Schnautz) Brown School, San Marcos, TX, United States. (Braverman) Path Medical Foundation, New York, NY, United States. (Schoolfield) Department of Academic Informatic Services, University of Texas, Health Science Center, San Antonio, TX, United States. (Downs) Allied Nutraceutical Research, Lederach, PA, United States. (Comings) Department of Medical Genetics, City of Hope National Medical Center, Duarte, CA, United States. Country of Publication United Kingdom Title Are dopaminergic genes involved in a predisposition to pathological aggression? Hypothesizing the importance of "super normal controls" in psychiatricgenetic research of complex behavioral disorders. Source Medical Hypotheses. 65(4)(pp 703-707), 2005. Date of Publication: 2005. Abstract We hypothesize that pathological aggression, a complex behavioral disorder, in adolescents may in part involve polymorphisms of the dopaminergic system. While a number of neurotransmitter systems must be involved, due to polygenic inheritance, one major pathway should involve the dopaminergic system. Advances in our knowledge of the neurobiology of aggression and violence have given rise to rational pharmacological treatments for these behaviors. The main biological systems that are known to be involved are certain reward neurotransmitters including: serotonin, opioid peptides, gamma-aminobutyric acid, and the catecholamines (dopamine and norepinephrine). It is our notion that pathological aggressive behavior is in part similar mechanistically to other forms of impulsive behaviors such as pathological gambling. By analogy to drug dependence, it has been speculated that the underlying pathology in pathological gambling is a reduction in the sensitivity of the reward system. While studying pathological gamblers and controls during a guessing game using functional Magnetic Resonance Imaging, Reuter et al. observed a reduction of ventral striatal and ventromedial prefrontal activation in the pathological gamblers that were negatively correlated with gambling severity. Subsequently, linking hypo activation of these areas to disease severity. A positive correlation of both the dopamine D2 receptor gene (DRD2) and the dopamine transporter gene (DAT1) polymorphisms were observed with pathological violence in adolescents in a blinded clinical trial. Thus, this and other cited work preliminary suggest a role for both the DRD2 and DAT genes in pathological aggressive behavior. We further hypothesize that follow-up gene research in this area, albeit premature, resulting in confirmation of positive correlations with dopaminergic polymorphisms, and utilizing highly screened controls (eliminating any addictive, compulsive and impulsive behaviors in both proband and family) may have important ramifications in our young population. copyright 2005 Elsevier Ltd. All rights reserved. ISSN 0306-9877 Publication Type Journal: Article Journal Name Medical Hypotheses Volume 65 Issue Part 4 Page 703-707 Year of Publication 2005 Date of Publication 2005

NEURO (PHARM) <234> Database EMBASE Accession Number 2005325215 Authors Ohlsen R.I. Pilowsky L.S. Institution (Ohlsen, Pilowsky) Institute of Psychiatry, De Crespigny Park, London SE5 8AF, United Kingdom. Country of Publication United Kingdom Title The place of partial agonism in psychiatry: Recent developments. Source Journal of Psychopharmacology. 19(4)(pp 408-413), 2005. Date of Publication: Jul 2005. Abstract Drugs used to treat psychiatric disorders, although effective, are often restricted by adverse events. The use of partial agonists for treating hypertension was found to limit some of the side-effects in some patients. This led to the investigation of partial agonists as a treatment modality in psychiatric disorders. Partial agonists have a lower intrinsic efficacy than full agonists leading to reduced maximum response. They can act as antagonists by competing for receptor binding with full agonists. The level of activity depends on the level of endogenous receptor activity. Buprenorphine, a partial agonist at the mu-opioid receptor, is used to treat patients with addiction and decreases the symptoms of withdrawal and risks of overdose and intoxication. The anxiolytic buspirone shows partial agonism at 5- HT_1A receptors, and this seems to provide anxioselective effects, without inducing extrapyramidal side-effects, convulsions, tolerance or withdrawal reactions. In schizophrenia, partial dopamine agonism results in antagonistic effects at sites activated by high concentrations of dopamine and agonistic effects at sites activated by low concentrations of dopamine. This stabilizes the dopamine system to effect antipsychotic action without inducing adverse motor or hormonal events. Aripiprazole is the first 'dopamine system stabilizer', and the data are promising, with efficacy at least equivalent to that with current atypical antipsychotics but fewer of the troublesome side-effects. Partial agonists seem to provide a way to fine-tune the treatment of psychiatric disorders by maximizing the treatment effect while minimizing undesirable adverse events. copyright 2005 British Association for Psychopharmacology. ISSN 0269-8811 Publication Type Journal: Review Journal Name Journal of Psychopharmacology Volume 19 Issue Part 4 Page 408-413 Year of Publication 2005 Date of Publication Jul 2005

NEURO (A) <235> Database EMBASE Accession Number 2005323562 Authors Chen R. Han D.D. Gu H.H. Institution (Chen, Han, Gu) Department of Pharmacology, Ohio State University College of Medicine, Columbus, OH, United States. (Gu) 333 West 10th Avenue, Columbus, OH 43210, United States. Country of Publication United Kingdom Title A triple mutation in the second transmembrane domain of mouse dopamine transporter markedly decreases sensitivity to cocaine and methylphenidate. Source Journal of Neurochemistry. 94(2)(pp 352-359), 2005. Date of Publication: Jul 2005. Abstract Previously, we reported that Phe105 in transmembrane domain 2 of the mouse dopamine transporter (DAT) is crucial for high-affinity cocaine binding. In the current study, we investigated whether other residues surrounding Phe105 also affect the potency of cocaine inhibition. After three rounds of sequential random mutagenesis at these residues, we found a triple mutant (L104V, F105C and A109V) of mouse DAT that retained over 50% uptake activity and was 69-fold less sensitive to cocaine inhibition when compared with the wild-type mouse DAT. The triple mutation also resulted in a 47-fold decrease in sensitivity to methylphenidate inhibition, suggesting that the binding sites for cocaine and methylphenidate may overlap. In contrast, the inhibition of dopamine uptake by amphetamine or methamphetamine was not significantly changed by the mutations, suggesting that the binding sites for the amphetamines differ from those for cocaine and methylphenidate. Such functional but cocaine-insensitive DAT mutants can be used to generate a knock-in mouse line to study the role of DAT in cocaine addiction. copyright 2005 International Society for Neurochemistry. ISSN 0022-3042 Publication Type Journal: Article Journal Name Journal of Neurochemistry Volume 94 Issue Part 2 Page 352-359 Year of Publication 2005 Date of Publication Jul 2005 NEURO <237> Database EMBASE Accession Number 2005319088 Authors Carlezon Jr. W.A. Duman R.S. Nestler E.J. Institution (Carlezon Jr.) Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA 02478, United States. (Duman) Department of Psychiatry, Yale University, School of Medicine, New Haven, CT 06508, United States. (Nestler) Department of Psychiatry, Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, United States. Country of Publication United Kingdom Title The many faces of CREB. Source Trends in Neurosciences. 28(8)(pp 436-445), 2005. Date of Publication: Aug 2005. Abstract The transcription factor CREB is best known for its involvement in learning and memory. However, emerging evidence suggests that CREB activity has very different roles - sometimes beneficial, sometimes detrimental - depending on the brain region involved. Induction of CREB in the hippocampus by antidepressant treatments could contribute to their therapeutic efficacy. By contrast, activation of CREB in the nucleus accumbens and several other regions by drugs of abuse or stress mediates certain aspects of drug addiction, and depressive and anxiety-like behaviors. These complexities suggest that strategies that exploit regional differences in upstream factors or that target specific CREB-regulated genes, rather than CREB itself, could make a promising contribution to the treatment of neuropsychiatric conditions. copyright 2005 Elsevier Ltd. All rights reserved. ISSN 0166-2236 Publication Type Journal: Review Journal Name Trends in Neurosciences Volume 28 Issue Part 8 Page 436-445 Year of Publication 2005 Date of Publication Aug 2005

NEURO (GENETICS) / AMPHETAMINES <255> Database EMBASE Accession Number 2005314897 Authors Ohgake S. Hashimoto K. Shimizu E. Koizumi H. Okamura N. Koike K. Matsuzawa D. Sekine Y. Inada T. Ozaki N. Iwata N. Harano M. Komiyama T. Yamada M. Sora I. Ujike H. Shirayama Y. Iyo M. Institution (Ohgake, Hashimoto, Shimizu, Koizumi, Okamura, Koike, Matsuzawa, Iyo) Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan. (Sekine) Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan. (Inada, Ozaki) Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan. (Iwata) Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan. (Harano) Department of Neuropsychiatry, Kurume University School of Medicine, Kurume, Japan. (Komiyama) National Center Hospital for Mental, Nervous and Muscular Disorders, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan. (Yamada) Division of Psychogeriatrics, National Institute of Mental Health, NCNP, Ichikawa, Japan. (Sora) Department of Psychobiology, University Graduate School of Medicine, Sendai, Japan. (Ujike) Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. (Shirayama) Department of Neuropsychiatry, Tottori University School of Medicine, Yonago, Japan. (Sekine, Inada, Ozaki, Iwata, Harano, Komiyama, Yamada, Sora, Ujike, Iyo) Japanese Genetics Initiative for Drug Abuse (JGIDA), Japan. (Hashimoto) Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260- 8670, Japan. Country of Publication United Kingdom Title Functional polymorphism of the NQO2 gene is associated with methamphetamine psychosis. Source Addiction Biology. 10(2)(pp 145-148), 2005. Date of Publication: Jun 2005. Abstract Several lines of evidence suggest that genetic factors contribute to the vulnerability of drug abuse such as methamphetamine (MAP), and that dopamine-quinones produced by administration of MAP may be involved in the mechanism of MAP-related symptoms. The detoxification of quinones is catalyzed by a family of proteins designated as quinone oxidoreductases (NQOs). We analysed the polymorphisms of NQO1 and NQO2 genes to elucidate the association with genetic vulnerability to MAP abuse in Japan. The genotype and allele frequencies for the polymorphism (Pro187Ser) of the NQO1 gene did not differ between each subgroup of patients and controls. In contrast, the genotype frequency for the insertion/deletion (I/D) polymorphism in the promoter region of the NQO2 gene was a significant (p = 0.038) difference between patients with prolonged-type MAP psychosis and controls. This study suggests that the NQO2 gene polymorphism contributes to the aetiology of MAP-related psychosis in Japanese. copyright Society for the Study of Addiction to Alcohol and Other Drugs. ISSN 1355-6215 Publication Type Journal: Article Journal Name Addiction Biology Volume 10 Issue Part 2 Page 145-148 Year of Publication 2005 Date of Publication Jun 2005

NEURO (A) <276> Database EMBASE Accession Number 2005297399 Authors Biala G. Betancur C. Mansuy I.M. Giros B. Institution (Biala, Betancur, Giros) INSERM U513, 8 rue du General Sarrail, 94010 Creteil Cedex, France. (Mansuy) Brain Research Institute, University of Zurich, Swiss Federal Institute of Technology, Zurich, Switzerland. (Biala) Department of Pharmacodynamics, Skubiszewski Medical University of Lublin, 4 Staszica Street, 20-081 Lublin, Poland. Country of Publication United Kingdom Title The reinforcing effects of chronic D-amphetamine and morphine are impaired in a line of memory-deficient mice overexpressing calcineurin. Source European Journal of Neuroscience. 21(11)(pp 3089-3096), 2005. Date of Publication: Jun 2005. Abstract It has recently emerged that there is a commonality in the molecular mechanisms underlying long-term neuronal changes in drug addiction and those mediating synaptic plasticity associated with learning and memory. In the hippocampus, the calcium-calmodulin- dependent protein phosphatase calcineurin plays a pivotal role in the molecular mechanisms that underlie learning and memory functions. Transgenic mice that express an active form of calcineurin specifically in forebrain structures have previously been shown to have a deficit in the transition from short- to long-term memory. Here, we investigated the involvement of calcineurin in the motivational effects of amphetamine and morphine using this line of transgenic mice (CN98). Our results showed that amphetamine and morphine did not induce conditioned place preference in calcineurin-mutant mice, whereas food remained an efficient reinforcer. In addition, behavioural sensitization to these two drugs, as measured by horizontal locomotion, was disturbed in the transgenic mice. In contrast, neither the horizontal locomotion in response to acute D-amphetamine or morphine nor the somatic signs of morphine withdrawal were affected in calcineurin mutant mice compared to their wild-type littermates. Our data indicate that calcineurin-mediated protein dephosphorylation in the hippocampus is involved in the long-term effects of drugs of abuse without influencing the motivational response to a natural reward or the physical component of opioid withdrawal. The present results emphasize the essential role of hippocampal-dependent learning and memory in the development of drug addiction. copyright Federation of European Neuroscience Societies. ISSN 0953-816X Publication Type Journal: Article Journal Name European Journal of Neuroscience Volume 21 Issue Part 11 Page 3089-3096 Year of Publication 2005 Date of Publication Jun 2005

NEURO (GENETICS) <278> Database EMBASE Accession Number 2005295500 Authors Goldman D. Oroszi G. Ducci F. Institution (Goldman, Oroszi, Ducci) Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852, United States. Country of Publication United Kingdom Title The genetics of addictions: Uncovering the genes. Source Nature Reviews Genetics. 6(7)(pp 521-532), 2005. Date of Publication: Jul 2005. Abstract The addictions are common chronic psychiatric diseases that today are prevented and treated using relatively untargeted and only partially effective methods. The addictions are moderately to highly heritable, which is paradoxical because these disorders require use; a choice that is itself modulated by both genes and environment. The addictions are interrelated and related to other psychiatric diseases by common neurobiological pathways, including those that modulate reward, behavioural control and the anxiety or stress response. Our future understanding of addictions will be enhanced by the identification of genes that have a role in altered substance-specific vulnerabilities such as variation in drug metabolism or drug receptors and a role in shared vulnerabilities such as variation in reward or stress resiliency. ISSN 1471-0056 Publication Type Journal: Review Journal Name Nature Reviews Genetics Volume 6 Issue Part 7 Page 521-532 Year of Publication 2005 Date of Publication Jul 2005 NEURO (A) <308> Database EMBASE Accession Number 2005275484 Authors Grueter B.A. Winder D.G. Institution (Grueter, Winder) Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, United States. (Winder) Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN, United States. (Winder) Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 724B Robinson Research Building, 23rd and Pierce Ave., Nashville, TN 37232-0615, United States. Country of Publication United Kingdom Title Group II and III metabotropic glutamate receptors suppress excitatory synaptic transmission in the dorsolateral bed nucleus of the stria terminalis. Source Neuropsychopharmacology. 30(7)(pp 1302-1311), 2005. Date of Publication: Jul 2005. Abstract Conditions such as anxiety, drug abuse, and post-traumatic stress disorder are thought to reflect alterations in central nervous system stress and reward circuitry. Recent evidence suggests a key component of this circuitry is the bed nucleus of the stria terminalis (BNST). In particular, regulation of glutamatergic transmission in the BNST plays a critical role in animal performance on anxiety tasks. Metabotropic glutamate receptors (mGluRs) have been implicated in stress and drug addiction and are known to regulate glutamatergic transmission in many brain regions. We have utilized both extracellular field potential and whole-cell patch- clamp recording in an in vitro slice preparation of mouse dorsal anterolateral BNST to determine whether G_i/o-linked mGluRs modulate excitatory transmission in this region. We find that activation of group II and group III mGluRs in an in vitro slice preparation of the dBNST causes a depression of excitatory transmission. The depression evoked by group II mGluR activation may represent a form of synaptic plasticity as prolonged activation of the receptor produces a long-term depression of glutamatergic transmission. Based on paired-pulse rado analysis, initiation of depression by group II and group III mGluR subfamilies appears to, at least in part, involve decreased glutamate release. In total, our data suggest a plausible site of action for some of the anxiolytic effects of group II and group III mGluR agonists. copyright 2005 Nature Publishing Group All rights reserved. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 30 Issue Part 7 Page 1302-1311 Year of Publication 2005 Date of Publication Jul 2005

NEURO <319> Database EMBASE Accession Number 2005260472 Authors Hokfelt T. Institution (Hokfelt) Department of Neuroscience, Karolinska Institutet, Retzius vag 8, S-171 77 Stockholm, Sweden. Country of Publication United Kingdom Title Galanin and its receptors: Introduction to the Third International Symposium, San Diego, California, USA, 21-22 October 2004. Source Neuropeptides. 39(3)(pp 125-142), 2005. Date of Publication: Jun 2005. Abstract The Third Galanin Symposium presented many different and exciting results on galanin research reflecting a major progress since the previous symposium in 1998. A major impression was the many possible relationships of galaninergic mechanisms to important brain functions such as development, cognition and ageing as well as many aspects related to a wide spectrum of diseases, including Alzheimer's disease, anxiety/depression, addiction, obesity, pain and tumour growth. These studies were based on an extensive armament of methodologies including various strains of transgenic mice. Unfortunately, the pharmaceutical industry had only a minor participation. Nevertheless, exciting developments in the generation of agonists and antagonists are emerging, providing hope that we at the next symposium will be able to validitate many of the challenging hypotheses concerning galanin and disease with the help of pharmacological tools. copyright 2005 Elsevier Ltd. All rights reserved. ISSN 0143-4179 Publication Type Journal: Conference Paper Journal Name Neuropeptides Volume 39 Issue Part 3 Page 125-142 Year of Publication 2005 Date of Publication Jun 2005

NEURO <338> Database EMBASE Accession Number 2005246002 Authors Andlin-Sobocki P. Jonsson B. Wittchen H.-U. Olesen J. Institution (Andlin-Sobocki) Stockholm Health Economics, Stockholm, Sweden. (Andlin-Sobocki) Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden. (Jonsson) Center for Health Economics, Stockholm School of Economics, Stockholm, Sweden. (Wittchen) Institute of Clinical Psychology and Psychotherapy, Technische Universitat Dresden, Dresden, Germany. (Olesen) Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark. (Andlin-Sobocki) Stockholm Health Economics, Klarabergsgatan 33, SE-111 21 Stockholm, Sweden. (Olesen) European Brain Council, Country of Publication United Kingdom Title Cost of disorders of the brain in Europe. Source European Journal of Neurology, Supplement. 12(SUPPL. 1)(pp i-27), 2005. Date of Publication: Jun 2005. Abstract Background: Brain disorders (psychiatric, neurological and neurosurgical diseases together) figure amongst the leading causes of disease and disability. Yet, the knowledge of the epidemiological and economic impact of brain disorders has been relatively little researched in Europe. WHO data suggest, however, that brain disorders cause 35% of the burden of all diseases in Europe. Objectives: The present study aims at estimating the economic cost of disorders of the brain in Europe based on the published epidemiological and economic evidence. A secondary objective was to identify gaps in both epidemiological and economic evidence on brain disorders thus providing focus for future research efforts. Methods: A model was developed to combine epidemiological and economic data on brain disorders in Europe (EU member countries, Iceland, Norway and Switzerland) and thus estimate their total cost. More specifically, it consisted of the following steps in which we: (i) transformed and converted available economic data to a defined time-period as well as currency ([euro]2004); (ii) adjusted country specific economic data for purchasing power and relative size of economy; (iii) imputed data for countries where no data are available; (iv) combined epidemiology and economic data to estimate the total cost of a defined disease; (v) added the cost of all selected disorders to arrive at the total cost for Europe. The model was populated with data collected from extensive literature reviews in the epidemiology and economic burden of brain disorders in Europe, conducted by 12 groups of European epidemiologists and health economists. The cost data were calculated as cost per patient, and epidemiological data were primarily reported as 12-month prevalence estimates. National and international statistics for the model were retrieved from the OECD (Organization for Economic Co-operation and Development) and Eurostat databases. The aggregated annual cost estimates were presented in Euros for 2004. Results: There are an estimated 127 million Europeans currently living with a brain disorder out of a population of 466 million. The total annual cost of brain disorders in Europe was estimated to [euro]386 billion in 2004. Direct medical expenditures alone totalled [euro]135 billion, comprising inpatient stays ([euro]78 billion), outpatient visits ([euro]45 billion) and drug costs ([euro]13 billion). Attributable indirect costs resulting from lost workdays and productivity loss because of permanent disability caused by brain disorders and mortality were [euro]179 billion, of which the mental disorders are the most prevalent. Direct non-medical costs (social services, informal care and other direct costs) totalled [euro]72 billion. Mental disorders amounted to [euro]240 billion and hence constitute 62% of the total cost (excluding dementia), followed by neurological diseases (excluding dementia) totalling [euro]84 billion (22%). Neurosurgical diseases made up a smaller fraction of the total cost of brain disorders in Europe, reaching a cost of [euro]8 billion. The average cost of brain disorders in Europe was [euro]829 per inhabitant (based on a total number of inhabitants in Europe of 466 million). However, the cost per inhabitant is different between European countries, and in general cost of brain disorders per inhabitant is higher in Western European countries compared with the EU admission countries. Because of scarcity of data, our total cost results only partially includes direct non-medical cost (e.g. community care and informal care) and indirect costs, and omits completely intangible costs. We have for example shown that the cost of dementia increase with 25% when including informal care and the cost of multiple sclerosis increases with at least 50% when including intangible costs. Discussion: The scarcity of both epidemiologic and health economic data in several countries and for specific brain disorders have led to conservative inclusions of cost items and population age groups. Together with the restriction of the present study to the most prevalent brain disorders this leads to the conclusion, that the true economic cost of disorders of the brain is substantially higher than our estimate of 386 billion Euros, perhaps in the range 500-700 billion Euros. Brain disorders are, thus, substantially more costly than other important fields of medicine such as heart disease, cancer and diabetes. However, the burden of brain disorders is seldom taken together, but rather reported by each single diagnosis. If training efforts, research funding and health care resources could be allocated according to this new knowledge, a very considerable increase in funding of brain related activities should take place. Our cost estimations are the best possible based on the economic and epidemiological data available in Europe today. However, our study has identified major shortcomings both in the epidemiological and economic evidence on brain disorders in Europe, in particular in the EU admission countries. More research of a systematic, prospective, collaborative nature is needed in order to accurately estimate the cost of disorders of the brain in Europe. Conclusion: Based on extensive literature reviews, the present study provides best possible estimates of the cost of disorders of the brain in Europe in 2004. In 28 countries with a population of 466 million, 127 million were affected by at least one brain disorder. The total annual cost was [euro]386 billion (386 000 000 00). Brain research funding, health care resource allocation and teaching at medical schools are proportionately much smaller. The huge cost and burden of brain disorders calls for increased efforts in research, health care and teaching. copyright 2005 EFNS. ISSN 1351-5101 Publication Type Journal: Review Journal Name European Journal of Neurology, Supplement Volume 12 Issue Part SUPPL. 1 Page i-27 Year of Publication 2005 Date of Publication Jun 2005 NEURO <348> Database EMBASE Accession Number 2005228315 Authors Kovacic P. Institution (Kovacic) Department of Chemistry, San Diego State University, 5500 Campanile Dr., San Diego, CA 92182-1030, United States. Country of Publication United Kingdom Title Unifying mechanism for addiction and toxicity of abused drugs with application to dopamine and glutamate mediators: Electron transfer and reactive oxygen species. Source Medical Hypotheses. 65(1)(pp 90-96), 2005. Date of Publication: 2005. Abstract There are many unknown aspects concerning the mode of action of abused drugs. Recently, a unifying theme for toxicity and addiction was reported based on electron transfer (ET), reactive oxygen species (ROS), and oxidative stress (OS). The main drugs involved are nicotine, cocaine, alcohol, phencyclidine, ecstasy, amphetamines, morphine-heroin, tetrahydrocannabinol, and therapeutic drugs (benzodiazepines, phenytoin, phenobarbital, aspirin, and acetaminophen). A major source of ROS is ET functionalities, of which the main ones found in abused drug metabolites are quinones and imines (or iminiums). Minor types are the nitroxide metabolite from cocaine, and alpha-dicarbonyl from alcohol. The theoretical approach enjoys support from reports on formation of ET metabolites, generation of ROS, protection by antioxidants (AOs), electrochemical studies, and cell signaling. Dopamine (DA) mediation of drug abuse has been the focus of much attention during the past decades. Recently, a similar role for glutamate (Glu) has come under study. Superficially, from a mechanistic vantage point, these findings might be regarded as in conflict with the ET-ROS- OS scheme. Many investigators believe that each drug or mediator operates by its own distinct mechanism. The present report provides evidence that a commonality in mode of action exists for both abused drugs and the DA-Glu operators. In the case of DA, oxidative metabolism yields o-quinones and semiquinones which can redox cycle with oxygen to provide various ROS. Electrochemical studies support the possibility of ET transformations by these quinones in the biological domain. In relation to cell signaling, DA is involved in formation of cAMP followed by a cascade of other events. A similar scenario exists in the case of Glu, in which an iminocarboxylic acid metabolite is hypothesized to play an ET role. The various phenomena are rationalized within the context of ET-ROS-OS, as was done earlier for abused drugs. Thus, a common mode of action may exist for both categories since all provide metabolites with similar properties. Stimulation of mediator production by abused drugs can occur with subsequent oxidation by ROS, some of which may be supplied by the drugs. In addition to prevention, the difficult topic of addiction mechanism is addressed from the viewpoint of ET and ROS involvement. Low levels of ROS would pertain since high concentrations are related to toxicity. A report that tetrahydrocannabinol does not comprise a substantial risk is in accord with little evidence of OS and absence of ET functionalities in the drug and reported metabolites. copyright 2005 Elsevier Ltd. All rights reserved. ISSN 0306-9877 Publication Type Journal: Article Journal Name Medical Hypotheses Volume 65 Issue Part 1 Page 90-96 Year of Publication 2005 Date of Publication 2005

NEURO (A) <380> Database EMBASE Accession Number 2005200559 Authors Wintermantel T.M. Berger S. Greiner E.F. Schutz G. Institution (Wintermantel, Berger, Greiner, Schutz) Molecular Biology of the Cell I, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. (Greiner) Evotec OAI AG, Schnackenburgallee 114, D-22525 Hamburg, Germany. Country of Publication United Kingdom Title Evaluation of steroid receptor function by gene targeting in mice. Source Journal of Steroid Biochemistry and Molecular Biology. 93(2-5)(pp 107-112), 2005. Date of Publication: Feb 2005. Abstract Corticosteroid hormones regulate a variety of developmental, physiological and pathological processes via their cognate receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Using modern genetic technologies, including bacterial artificial chromosome-based transgenesis and conditional gene targeting, we have generated a panel of tissue-specific and function-selective mutations of the two corticosteroid hormone receptors in the mouse. These mouse models have allowed us to gain new insights into corticosteroid hormone signaling in vivo. By investigating a hepatocyte-specific GR mutation, it has been possible to define a novel biological action of GR, namely to function as a coactivator for Stat5-mediated gene transcription in the control of body growth. The investigation of brain-specific mutations have not only allowed us to better understand hypothalamo-pituitary-adrenal (HPA) axis regulation by glucocorticoids, but also to analyse corticosteroid action in various aspects of brain function like anxiety-related or addiction- related behaviour, and learning and memory. A function-selective mutation in the GR has allowed us to dissect different pathways in the gene expression regulation by this receptor, namely to separate DNA response element-binding dependent gene activation from response element-independent gene regulation via interference with other transcription factors. These different transcriptional activities of GR play an important role in glucocorticoid-mediated immunosuppression. copyright 2005 Elsevier Ltd. All rights reserved. ISSN 0960-0760 Publication Type Journal: Conference Paper Journal Name Journal of Steroid Biochemistry and Molecular Biology Volume 93 Issue Part 2-5 Page 107-112 Year of Publication 2005 Date of Publication Feb 2005