DOCSLIB.ORG

The Effect of Nucleus Accumbens Lesions On

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Effect of Nucleus Accumbens Lesions On Research Article • DOI: 10.2478/s13380-013-0146-x • Translational Neuroscience • 4(4) • 2013 • 419-428 Translational Neuroscience THE EFFECT OF NUCLEUS Yarong Wang#1, Jia Zhu#1, ACCUMBENS LESIONS ON Ling Chen2, Yijun Liu3, Qiang Li1, APPETITE, SEXUAL FUNCTION, Weichuan Yang1, Wei Li1, AND NICOTINE DEPENDENCE IN Liyan Zhao4, Mark S. Gold3, Jifeng Sun5*, RECOVERING HEROIN ADDICTS Wei Wang1* Abstract 1 Department of Radiology, Tangdu Hospital, The nucleus accumbens (NAc) is a key part of the neural circuitry that creates reward, pleasure and motivation the Fourth Military Medical University, 569 that facilitates human feeding, sexual and smoking behaviors. In the brain reward system, the NAc is a crucial Xinsi Road, Baqiao District, Xi’an 710038, component responsible for natural and drug-induced reinforcement behaviors. Yet it is unclear whether NAc is China. indispensible for all reward behaviors in human beings. The present study aimed to investigate the long-term 2 Department of Oncology, the First effects of NAc ablation on sexual function, appetite, and nicotine dependence level in chronic heroin users. Aliated Hospital of Xi’an Jiaotong Eighteen former heroin–dependent patients (male) with bilateral NAc ablation via stereotactic radiofrequency University, 766 West Yantan Road, Xi’an surgery for alleviating drug psychological dependence were recruited. Their postoperative time ranged from 12 710061, China. to 103 months. All subjects received MRI scans for assessing the accuracy of the lesion site. Evaluation of appetite, 3 Department of Psychiatry, University of sexual function, and nicotine dependence were measured using the Simplified Nutrition Appetite Questionnaire, Florida College of Medicine, 100 Newell Dr the Brief Sexual Function Inventory, and the Fagerström Test for Nicotine Dependence, respectively. After L4100, Gainesville, Florida 32610, USA. precluding the potential confounding variables, such as drug use (dosage and duration), post-operation 4 National Institute on Drug Dependence, duration, age, body-weight, marital status and education level, ANOVA with repeated measures revealed that Peking University, 38 Xueyuan Road, the NAc ablation improved the patients’ appetite, sexual drive and sexual satisfaction. Yet there was no change in Beijing 100083, China. male erectile function, ejaculatory function, or nicotine dependence levels compared to the preoperative. These 5 Department of Nephrology, Tangdu may suggest that although NAc is a key part of the neural circuitry, the NAc surgical lesions left the fundamental Hospital, the Fourth Military Medical aspects of natural and drug-induced reinforcement and motivation almost intact. University, 569 Xinsi Road, Baqiao District, Keywords Xi’an 710038, China. • Nucleus accumbens (NAc) • Heroin dependence • Human reward behavior Received 18 July 2013 accepted 02 December 2013 © Versita Sp. z o.o. Introduction conditioning [12], so it is of great significance to in the reinforcing action of primary reinforcers explore the relationship between the NAc and and illicit drugs. In human and animal brains there exists a specific human reward behaviors. To investigate the functional role of NAc reward mechanism that serves to maintain In this system, especially in the NAc, in human reward behaviors, scholars have and encourage the motivations and activities dopamine (DA) predominantly mediates the employed multiple approaches, including beneficial for survival and reproduction. primary reinforcing characteristics of natural neuroanatomical [22], electrophysiological The neural substrate underlying the reward rewards (such as food and sex), in addition to [23], intracranial microinjection [24] and mechanism is mainly based on the meso- those of drug abuse and addiction [13]. When a neuroimaging methods [25]. The intracranial corticolimbic dopaminergic pathway that natural reinforcer or drug of abuse is consumed, microinjection can identify neural circuitry and originates in the midbrain ventral tegmental extracellular DA concentration in the NAc is explore the reward effects of multiple chemical area (VTA) with projections to the nucleus increased, which is associated with the feeling transmitters, but cannot directly analyze the accumbens (NAc) and connections with other of “euphoria” [13-15]. When anticipating or neural transmission involved in humans [24]. brain regions, including the amygdala, ventral actually consuming the reinforcer [13,16,17] Functional neuroimaging is a powerful tool to pallidum, dorsal striatum, hippocampus and or when activated to encode saliency of a reveal the brain regions associated with reward prefrontal cortex [1]. Ample evidence confirms given stimulant [17-20], the NAc can also responses [25], but it cannot determine which that almost all drugs of abuse (heroin, cocaine, release DA, facilitating the reward behaviors. brain area is essential for reward behavior. morphine, amphetamine) may dysregulate this It is noteworthy that a natural reinforcer Studies of patients with NAc lesions are system, inducing the development of addiction differs from drugs of abuse in reinforcing unique in enabling us to examine the specific [2-6]. Further, natural reward and drug abuse action. The primary difference lies in that the NAc-behavior relationships [22]. To date, few share this neural circuitry to accomplish the latter can modify the kinetics and amplitude studies have explored the effects of NAc lesions reinforcement effects [7-11]. In this neural of the dopamine release and form memories on reward behavior in humans. The most circuitry NAc plays an important role in associated with drug consumption [21]. Such notable to mention are a case study [26] and reward/saliency, motivation/drive, memory/ evidence shows that the NAc has a pivotal role two studies in which NAc lesions extensively * E-mail: [email protected] ; [email protected] # These two authors contributed to this work equally. 419 Translational Neuroscience involved adjacent brain structures [27,28]. daily methadone dose. All the participants were The post-surgery follow-up was regularly The lack of literature on specific NAc lesions required to have a urine toxicology screening conducted via telephone after a 6-month makes it difficult to do a clinical-pathological test at the time of study enrollment. interval. Our investigators focused on the correlation analysis to human NAc lesions. Exclusion criteria included: a) incorrect patients’ physical, psychological, neurological The objective of this study was to better NAc target site or lesions that involved an and psychiatric information, especially their understand the structure-function relationship adjacent brain structure according to the MRI illicit drug use. These data were obtained of the NAc by identifying the relations between data (see “Accuracy assessment of ablation via patient self-report or the report of their the NAc and specific reward behaviors in a site”); b) current or past psychiatric illness families living with them. When the patients group of patients who underwent bilateral NAc other than heroin dependence; c) neurological encountered any health problem and sought ablation by stereotactic surgery for alleviating signs, severe mental disorder, or intelligence further medical treatment, physical and opiate drug psychological dependence. dysfunction; d) current medical illness; e) imaging examinations were available. After a Specifically, we investigated the long-term dependence on any other psychoactive period (1~7 years), there were 22 patients lost inuence of bilateral NAc ablation on natural substance other than nicotine or coffee; f) to follow up. Among the remaining 20 patients, reward (appetite, sexual behavior) and drug history of head trauma; and g) MRI examination 19 had no MRI scan contraindication and were reward (nicotine dependence) in these patients. contraindication. None of the participants willing to take part in the present study. experienced strong withdrawal symptoms All telephone interviews were conducted Materials and methods during the study. 1 participant was excluded by 3 highly experienced interviewers in social because the brain structure MRI scan revealed and psychiatric research. The telephone The ethics statement and study that his NAc lesions involved an adjacent conversation was recorded during the population structure. Eventually, 18 participants entered telephone interview. And at least half of the live This study followed the principles outlined in the next analyses. conversations were monitored in real time by a the Declaration of Helsinki (6th revised version, supervisor to ensure the reliability and validity Edinburgh, 2000). Ethics approval was obtained Background of the study population of survey data. from the Ethics Committee of the Fourth and their follow-up investigation Military Medical University (at the Review From 2002 to 2008, a clinical study was Experimental procedures Board Meeting held on 18th March 2002) and conducted to explore a new way to alleviate Tangdu Hospital Ethic Committee (approval opiate drug psychological dependence by All participants were well informed about the no. TDLL-2009039 from 5th March 2009). The ablating the NAc with stereotactic surgery in study and gave their consents to the surgical authors declare no conflict of interest. China [29]. There were a total of 42 intractable treatment, the post-surgery MRI scan for Nineteen of 42 male chronic heroin heroin dependent patients who underwent verifying the lesion loci and the questionnaire
Load more

Recommended publications
  • Neuromodulators and Long-Term Synaptic Plasticity in Learning and Memory: a Steered-Glutamatergic Perspective
    brain sciences Review Neuromodulators and Long-Term Synaptic Plasticity in Learning and Memory: A Steered-Glutamatergic Perspective Amjad H. Bazzari * and H. Rheinallt Parri School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK; [email protected] * Correspondence: [email protected]; Tel.: +44-(0)1212044186 Received: 7 October 2019; Accepted: 29 October 2019; Published: 31 October 2019 Abstract: The molecular pathways underlying the induction and maintenance of long-term synaptic plasticity have been extensively investigated revealing various mechanisms by which neurons control their synaptic strength. The dynamic nature of neuronal connections combined with plasticity-mediated long-lasting structural and functional alterations provide valuable insights into neuronal encoding processes as molecular substrates of not only learning and memory but potentially other sensory, motor and behavioural functions that reflect previous experience. However, one key element receiving little attention in the study of synaptic plasticity is the role of neuromodulators, which are known to orchestrate neuronal activity on brain-wide, network and synaptic scales. We aim to review current evidence on the mechanisms by which certain modulators, namely dopamine, acetylcholine, noradrenaline and serotonin, control synaptic plasticity induction through corresponding metabotropic receptors in a pathway-specific manner. Lastly, we propose that neuromodulators control plasticity outcomes through steering glutamatergic transmission, thereby gating its induction and maintenance. Keywords: neuromodulators; synaptic plasticity; learning; memory; LTP; LTD; GPCR; astrocytes 1. Introduction A huge emphasis has been put into discovering the molecular pathways that govern synaptic plasticity induction since it was first discovered [1], which markedly improved our understanding of the functional aspects of plasticity while introducing a surprisingly tremendous complexity due to numerous mechanisms involved despite sharing common “glutamatergic” mediators [2].
    [Show full text]
  • Multiplexed Neurochemical Signaling by Neurons of the Ventral Tegmental
    Journal of Chemical Neuroanatomy 73 (2016) 33–42 Contents lists available at ScienceDirect Journal of Chemical Neuroanatomy journal homepage: www.elsevier.com/locate/jchemneu Multiplexed neurochemical signaling by neurons of the ventral tegmental area David J. Barker, David H. Root, Shiliang Zhang, Marisela Morales* Neuronal Networks Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse, 251 Bayview Blvd Suite 200, Baltimore, MD 21224, United States A R T I C L E I N F O A B S T R A C T Article history: The ventral tegmental area (VTA) is an evolutionarily conserved structure that has roles in reward- Received 26 June 2015 seeking, safety-seeking, learning, motivation, and neuropsychiatric disorders such as addiction and Received in revised form 31 December 2015 depression. The involvement of the VTA in these various behaviors and disorders is paralleled by its Accepted 31 December 2015 diverse signaling mechanisms. Here we review recent advances in our understanding of neuronal Available online 4 January 2016 diversity in the VTA with a focus on cell phenotypes that participate in ‘multiplexed’ neurotransmission involving distinct signaling mechanisms. First, we describe the cellular diversity within the VTA, Keywords: including neurons capable of transmitting dopamine, glutamate or GABA as well as neurons capable of Reward multiplexing combinations of these neurotransmitters. Next, we describe the complex synaptic Addiction Depression architecture used by VTA neurons in order to accommodate the transmission of multiple transmitters. Aversion We specifically cover recent findings showing that VTA multiplexed neurotransmission may be mediated Co-transmission by either the segregation of dopamine and glutamate into distinct microdomains within a single axon or Dopamine by the integration of glutamate and GABA into a single axon terminal.
    [Show full text]
  • Midbrain Dopaminergic and Gabaergic Neurons' Responses To
    Institute of Zoology and Biomedical Research Topic: Midbrain dopaminergic and GABAergic neurons' responses to the aversive stimulus across alternating brain states of urethane anaesthetized rat - electrophysiological in vivo studies. Supervisor: dr hab. Tomasz Błasiak (Department of Neurophysiology and Chronobiology) [email protected] Background information: Ventral tegmental area (VTA) is one of the main sources of dopamine (DA) in the mammalian brain. This structure is the centre of dopaminergic pathways and plays a key role in regulation of motivation (Wise, 2005), goaldirected behaviours, reinforcement learning or reacting to reward-related cues (Schultz, 1997; Morita, 2013). Better understanding of how DA circuits work and are modulated can contribute to explanation of mechanisms of dysfunctions laying at the root of some nervous system disorders such as addiction, anxiety, PTSD or some of depression symptoms (anhedonia or lack of motivation). It has been shown that, occurrence of unexpected reward, reward-related cue or novelty causes phasic release of DA in VTA target structures (Goto et al, 2007). Those phasic changes in DA neurons activity lie at the root of forming reward prediction error (RPE) signal which encodes difference between expected and delivered reward - updating reward expectations and forming the basis for learning (Schultz, 2016). DA neurons also code response to the aversive or noxious stimuli by development of quick, short latency pause in firing. For a long time, it has been assumed that DA neurons code both reward and aversive stimuli homogenously across the entire dopaminergic neurons population forming positive and negative prediction error signals respectively (Schultz, 1998; Ungless et al., 2004).
    [Show full text]
  • Chronic Amphetamine Exposure Causes Long Term Effects on Dopamine Uptake in Cultured Cells Nafisa Ferdous
    University of North Dakota UND Scholarly Commons Theses and Dissertations Theses, Dissertations, and Senior Projects January 2016 Chronic Amphetamine Exposure Causes Long Term Effects On Dopamine Uptake In Cultured Cells Nafisa Ferdous Follow this and additional works at: https://commons.und.edu/theses Recommended Citation Ferdous, Nafisa, "Chronic Amphetamine Exposure Causes Long Term Effects On Dopamine Uptake In Cultured Cells" (2016). Theses and Dissertations. 2016. https://commons.und.edu/theses/2016 This Thesis is brought to you for free and open access by the Theses, Dissertations, and Senior Projects at UND Scholarly Commons. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of UND Scholarly Commons. For more information, please contact [email protected]. CHRONIC AMPHETAMINE EXPOSURE CAUSES LONG TERM EFFECTS ON DOPAMINE UPTAKE IN CULTURED CELLS By Nafisa Ferdous Bachelor of Science, North South University, Bangladesh 2012 A Thesis submitted to the Graduate Faculty of the University of North Dakota in partial fulfillment of the requirements for the degree of Master of Science Grand Forks, North Dakota December 2016 ii PERMISSION Title Chronic amphetamine exposure causes long term effects on dopamine uptake in cultured cells Department Biomedical Sciences Degree Master of Science In presenting this thesis in partial fulfillment of the requirements for a graduate degree from the University of North Dakota, I agree that the library of this University shall make it freely available for inspection. I further agree that permission for extensive copying for scholarly purposes may be granted by the professor who supervised my thesis work or, in his absence, by the Chairperson of the department or the Dean of the School of Graduate Studies.
    [Show full text]
  • Dopaminergic Microtransplants Into the Substantia Nigra of Neonatal Rats with Bilateral 6-OHDA Lesions
    The Journal of Neuroscience, May 1995, 15(5): 3548-3561 Dopaminergic Microtransplants into the Substantia Nigra of Neonatal Rats with Bilateral 6-OHDA Lesions. I. Evidence for Anatomical Reconstruction of the Nigrostriatal Pathway Guido Nikkhah,1,2 Miles G. Cunningham,3 Maria A. Cenci,’ Ronald D. McKay,4 and Anders Bj6rklund’ ‘Department of Medical Cell Research, University of Lund, S-223 62 Lund, Sweden, *Neurosurgical Clinic, Nordstadt Hospital, D-301 67 Hannover, Germany, 3Harvard Medical School, Boston, Massachusetts 02115, and 4 Laboratory of Molecular Biology, NINDS NIH, Bethesda, Maryland 20892 Reconstruction of the nigrostriatal pathway by long axon [Key words: target reinnervation, axon growth, neural growth derived from dopamine-rich ventral mesencephalic transplantation, tyrosine hydroxylase immunohistochem- (VM) transplants grafted into the substantia nigra may en- istry, Fos protein, Fluoro-Gold] hance their functional integration as compared to VM grafts implanted ectopically into the striatum. Here we report on In the lesioned brain of adult recipients dopamine-rich grafts a novel approach by which fetal VM grafts are implanted from fetal ventral mesencephalon (VM) are unable to reinner- unilaterally into the substantia nigra (SN) of 6-hydroxydo- vate the caudate-putamen unless they are placed close to, or pamine (SOHDA)-lesioned neonatal pups at postnatal day within, the denervated target structure (BjGrklund et al., 1983b; 3 (P3) using a microtransplantation technique. The results Nikkhah et al., 1994b). The failure of regenerating dopaminergic demonstrate that homotopically placed dopaminergic neu- axons to reinnervate the striatum from more distant implantation rons survive and integrate well into the previously sites, including their normal site of origin, the substantia nigra 6-OHDA-lesioned neonatal SN region.
    [Show full text]
  • Opiate Influences on Nucleus Accumbens Neuronal Electrophysiology: Dopamine and Non-Dopamine Mechanisms
    The Journal of Neuroscience, October 1969, 9(10): 35363546 Opiate Influences on Nucleus Accumbens Neuronal Electrophysiology: Dopamine and Non-Dopamine Mechanisms Ft. L. Hakan and S. J. Henriksen Department of Neuropharmacology, Research Institute of the Scripps Clinic, La Jolla, California 92037 Single-unit recordings of nucleus accumbens septi (NAS) abuse potential for humans such as the opiate alkaloids (Goeders neurons in halothane-anesthetized rats revealed that mi- et al., 1984; Vaccarino et al., 1985; Corrigal and Vaccarino, croinfusions of morphine into the ventral tegmental area (VTA) 1988; Koob and Goeders, 1989). Although there is controversy primarily inhibited spontaneously active NAS units. These regarding the precise neuropharmacological mechanism(s) un- inhibitory effects were reversed by alpha-flupenthixol (s.c.), derlying opiate actions on the NAS and on NAS-related brain suggesting a role for dopamine (DA) in the observed opiate- circuitry (e.g., see Wise, 1987), behavioral research has indicated induced effect. VTA opiate microinfusions also inhibited the that these drugs may exert pharmacological influence over NAS evoked (driven) responses of silent cells (spontaneously function via dopamine (DA)-dependent and DA-independent inactive) in the NAS elicited by stimulation of hippocampal projections from the DA containing cell bodies of the midbrain afferents to the NAS. In addition, this inhibition of driven ventral tegmental area (VTA) (Bozarth and Wise, 198 l), the response was reversed by naloxone (s.c.) but not by alpha- cellular origin of the DA-ergic input to the NAS (see Kelly et flupenthixol, implying a VTA-mediated non-DA mechanism. al., 1980; Stinus et al., 1980; Kalivas et al., 1983; Pettit et al., Morphine applied iontophoretically to cells within the NAS 1984; Amahic and Koob, 1985; Vaccarino et al., 1986; Wise, inhibited spontaneous activity but not fimbria-driven cellular 1987; Di Chiara and Imperato, 1988; Koob and Goeders, 1989).
    [Show full text]
  • Prominence of the Dopamine D2 Short Isoform in Dopaminergic Pathways
    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 7731–7736, June 1998 Neurobiology Prominence of the dopamine D2 short isoform in dopaminergic pathways ZAFAR U. KHAN*†,LADISLAV MRZLJAK*, ANTONIA GUTIERREZ‡,ADELAIDA DE LA CALLE‡, AND PATRICIA S. GOLDMAN-RAKIC* *Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510; and ‡Department of Cell Biology, University of Malaga, Malaga 29071, Spain Contributed by P. S. Goldman-Rakic, April 15, 1998 ABSTRACT As a result of alternative splicing, the D2 gene opment. Affinity purification of the antisera was as described of the dopamine receptor family exists in two isoforms. The D2 elsewhere (12). In brief, peptide (5 mg) was coupled to1gof long is characterized by the insertion of 29 amino acids in the activated thiopropyl-Sepharose 6B (Pharmacia LKB). Phos- third cytoplasmic loop, which is absent in the short isoform. We phate-buffered saline (PBS) diluted antiserum (1:5) was circu- have produced subtype-specific antibodies against both the D2 lated through the column. After washing with PBS, the antibody short and D2 long isoforms and found a unique compartmen- was eluted with glycinezHCl, pH 2.3, and dialyzed against PBS. talization between these two isoforms in the primate brain. The Membrane Preparation. Adult rhesus monkey (Macaca mu- D2 short predominates in the cell bodies and projection axons of latta) brains were used for the preparation of tissue membranes the dopaminergic cell groups of the mesencephalon and hypo- as described earlier (13). Briefly, brain tissues were homogenized thalamus, whereas the D2 long is more strongly expressed by with 10% sucrose in TriszHCl, pH 7.4, and centrifuged at 3,000 neurons in the striatum and nucleus accumbens, structures rpm in a Sorvall for 5 min.
    [Show full text]
  • Distribution of Dopamine D3 Receptor Expressing Neurons in the Human Forebrain: Comparison with D2 Receptor Expressing Neurons Eugenia V
    Distribution of Dopamine D3 Receptor Expressing Neurons in the Human Forebrain: Comparison with D2 Receptor Expressing Neurons Eugenia V. Gurevich, Ph.D., and Jeffrey N. Joyce, Ph.D. The dopamine D2 and D3 receptors are members of the D2 important difference from the rat is that D3 receptors were subfamily that includes the D2, D3 and D4 receptor. In the virtually absent in the ventral tegmental area. D3 receptor rat, the D3 receptor exhibits a distribution restricted to and D3 mRNA positive neurons were observed in sensory, mesolimbic regions with little overlap with the D2 receptor. hormonal, and association regions such as the nucleus Receptor binding and nonisotopic in situ hybridization basalis, anteroventral, mediodorsal, and geniculate nuclei of were used to study the distribution of the D3 receptors and the thalamus, mammillary nuclei, the basolateral, neurons positive for D3 mRNA in comparison to the D2 basomedial, and cortical nuclei of the amygdala. As revealed receptor/mRNA in subcortical regions of the human brain. by simultaneous labeling for D3 and D2 mRNA, D3 mRNA D2 binding sites were detected in all brain areas studied, was often expressed in D2 mRNA positive neurons. with the highest concentration found in the striatum Neurons that solely expressed D2 mRNA were numerous followed by the nucleus accumbens, external segment of the and regionally widespread, whereas only occasional D3- globus pallidus, substantia nigra and ventral tegmental positive-D2-negative cells were observed. The regions of area, medial preoptic area and tuberomammillary nucleus relatively higher expression of the D3 receptor and its of the hypothalamus. In most areas the presence of D2 mRNA appeared linked through functional circuits, but receptor sites coincided with the presence of neurons co-expression of D2 and D3 mRNA suggests a functional positive for its mRNA.
    [Show full text]
  • 1 Development of Methods for Measurement of the Integrity Of
    Development of Methods for Measurement of the Integrity of Dopaminergic Pathways in a Rat Model of Parkinson’s Disease1 ¢¡¤£¦¥¨§ © ¨ § £ Department of Cognitive Science, Carleton University [email protected] Bruce Hutcheon Department of Neuroscience, Carleton University [email protected] Introduction Parkinson’s disease (PD) is a progressive neurological disorder manifested by difficulty initiating movement, muscular rigidity, resting tremor, and other postural abnormalities. It is associated with a loss of neurons in the midbrain that supply the forebrain with dopamine. The resulting chemical deficit in forebrain structures results in a disruption of integrated motor output. Before a description of the experimental studies is given, an outline of the anatomy and basic operation of the motor circuits is needed. The regions of the brain that participate in voluntary movements are the basal ganglia, motor nuclei of the brain stem, red nucleus, and cerebellum. The region of interest in the case of PD is the basal ganglia. 1. The basal ganglia consists of four subcortical nuclei (see Figure 1): striatum [ST] (a collective term for the caudate nucleus and putamen), 2. globus pallidus (consisting of external [GPe] and internal segments [GPi]), 3. subthalamic nucleus [STN], and 4. substantia nigra [SN] (consisting of the pars compacta [SNc] and pars reticulata [SNr]). 1 Report Carleton University Cognitive Science Technical 2002-08 URL http://www.carleton.ca/iis/TechReports © 2002 Edina ¦ ! "¦#$&%('*)+-, .0/21$,34.05(/0% 1 Figure 1: Coronal section of the basal ganglia (adapted from Nieuwenhuys et al. 1981) These nuclei participate in a feedback loop which begins at the motor cortex, proceeds through the basal ganglia (with the striatum as the input centre), to the thalamus (the main conduit for sensory information reaching the brain), and back to the motor cortex.
    [Show full text]
  • Harnessing Serotonergic and Dopaminergic Pathways for Lymphoma Therapy: Evidence and Aspirations Nicholas M
    Seminars in Cancer Biology 18 (2008) 218–225 Review Harnessing serotonergic and dopaminergic pathways for lymphoma therapy: Evidence and aspirations Nicholas M. Barnes a, , John Gordon b a Division of Neuroscience, The Medical School, Vincent Drive, Birmingham B15 2TT, United Kingdom b Division of Immunity & Infection, The Medical School, Vincent Drive, Birmingham B15 2TT, United Kingdom Abstract Growing evidence supports the notion that pharmaceutical targeting of the 5-hydroxytryptamine (5-HT) and dopamine (DA) systems offers the potential to treat human immune system disorders. This review describes this emerging area of research, which has the benefit of being supported by a relatively detailed understanding of these monoamine systems within other tissues of the body. Furthermore, the availability of a number of pharmaceutical agents originally developed to manipulate central monoamine function, offer many suitable drug candidates to test their therapeutic potential in the immune pathology arena. © 2008 Published by Elsevier Ltd. Keywords: Lymphoma; Novel drug targets; Serotonin; Dopamine; Drug reprofiling Contents 1. Introduction ............................................................................................................ 218 2. 5-HT—the serotonergic pathway.......................................................................................... 219 2.1. Synthesis and metabolism of 5-HT.................................................................................. 219 2.2. 5-HT receptors and transporter ....................................................................................
    [Show full text]
  • 6950.Full.Pdf
    6950 • The Journal of Neuroscience, July 2, 2008 • 28(27):6950–6959 Behavioral/Systems/Cognitive Functional Interaction between the Hippocampus and Nucleus Accumbens Shell Is Necessary for the Acquisition of Appetitive Spatial Context Conditioning Rutsuko Ito,1,3 Trevor W. Robbins,1 Cyriel M. Pennartz,2 and Barry J. Everitt1 1Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom, 2Graduate School Neurosciences Amsterdam, University of Amsterdam, Faculty of Science, Swammerdam Institute for Life Sciences, 1098 SM Amsterdam, The Netherlands, and 3Department of Experimental Psychology, University of Oxford, Oxford OX1 3UD, United Kingdom The nucleus accumbens (NAc) has been implicated in a variety of associative processes that are dependent on the integrity of the amygdala and hippocampus (HPC). However, the extent to which the two subregions of the NAc, the core and shell, form differentiated circuits within the amygdala- and hippocampal-ventral striatal circuitry remains unclear. The present study investigated the effects of selective excitotoxic lesions of the nucleus accumbens shell or core subregion on appetitive elemental cue and context conditioning, shown previously to be dependent on the basolateral amygdala and hippocampus, respectively. Rats were trained sequentially to acquire discrete conditioned stimulus–sucrose conditioning, followed by spatial context–sucrose conditioning in a place preference apparatus characterized by three topographically identical chambers, the chambers being discriminable only on the basis of path integration. NAc shell lesions selectively impaired the acquisition of conditioned place preference and the use of spatial information to retrieve informa- tion about a discrete cue, whereas, as expected, NAc core lesions attenuated the acquisition of cue conditioning compared with sham rats.
    [Show full text]
  • Region-Dependent Dynamics of Camp Response Element-Binding Protein Phosphorylation in the Basal Ganglia
    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 4708–4713, April 1998 Neurobiology Region-dependent dynamics of cAMP response element-binding protein phosphorylation in the basal ganglia FU-CHIN LIU* AND ANN M. GRAYBIEL†‡ *Department of Life Sciences and Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan 11221 Republic of China; and †Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, E25-618, 45 Carleton Street, Cambridge, MA 02139 Contributed by Ann M. Graybiel, February 5, 1998 ABSTRACT The cAMP response element-binding protein pus, and the limbic prefrontal cortex, and projects back to (CREB) is an activity-dependent transcription factor that is limbic structures via the ventral pallidum. These limbic- involved in neural plasticity. The kinetics of CREB phosphor- associated circuits are thought to underlie motivational and ylation have been suggested to be important for gene activa- viscero-affective aspects of neurologic function served by the tion, with sustained phosphorylation being associated with ventral striatum. The midbrain dopamine pathways innervat- downstream gene expression. If so, the duration of CREB ing the dorsal and ventral striatum are critically involved in phosphorylation might serve as an indicator for time-sensitive controlling these functions, including, for the ventral striatum, plastic changes in neurons. To screen for regions potentially the reinforcing properties of psychostimulant and other drugs involved in dopamine-mediated plasticity in the basal ganglia, (3). we used organotypic slice cultures to study the patterns of A distinct feature of much reinforcement-based learning is dopamine- and calcium-mediated CREB phosphorylation in that the modified behaviors develop with time and are highly sensitive to the temporal organization of events (4, 5).
    [Show full text]