Insights Into Pathophysiology of Punding Reveal Possible Treatment
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Selective Labeling of Serotonin Receptors Byd-[3H]Lysergic Acid
Proc. Nati. Acad. Sci. USA Vol. 75, No. 12, pp. 5783-5787, December 1978 Biochemistry Selective labeling of serotonin receptors by d-[3H]lysergic acid diethylamide in calf caudate (ergots/hallucinogens/tryptamines/norepinephrine/dopamine) PATRICIA M. WHITAKER AND PHILIP SEEMAN* Department of Pharmacology, University of Toronto, Toronto, Canada M5S 1A8 Communicated by Philip Siekevltz, August 18,1978 ABSTRACT Since it was known that d-lysergic acid di- The objective in this present study was to improve the se- ethylamide (LSD) affected catecholaminergic as well as sero- lectivity of [3H]LSD for serotonin receptors, concomitantly toninergic neurons, the objective in this study was to enhance using other drugs to block a-adrenergic and dopamine receptors the selectivity of [3HJISD binding to serotonin receptors in vitro by using crude homogenates of calf caudate. In the presence of (cf. refs. 36-38). We then compared the potencies of various a combination of 50 nM each of phentolamine (adde to pre- drugs on this selective [3H]LSD binding and compared these clude the binding of [3HJLSD to a-adrenoceptors), apmo ie, data to those for the high-affinity binding of [3H]serotonin and spiperone (added to preclude the binding of [3H[LSD to (39). dopamine receptors), it was found by Scatchard analysis that the total number of 3H sites went down to 300 fmol/mg, compared to 1100 fmol/mg in the absence of the catechol- METHODS amine-blocking drugs. The IC50 values (concentrations to inhibit Preparation of Membranes. Calf brains were obtained fresh binding by 50%) for various drugs were tested on the binding of [3HLSD in the presence of 50 nM each of apomorphine (A), from the Canada Packers Hunisett plant (Toronto). -
Ergot Alkaloids As Dopamine Agonists: Comparison in Two Rodent Models
European Journal of Pharmacology, 37 (1976) 295-302 295 © North-Holland Publishing Company, Amsterdam - Printed in The Netherlands ERGOT ALKALOIDS AS DOPAMINE AGONISTS: COMPARISON IN TWO RODENT MODELS GILL ANLEZARK, CHRIS PYCOCK and BRIAN MELDRUM Department of Neurology, Institute of Psychiatry, Denmark Hill, London, SE5 8AF, U.K. Received 18 December 1975, revised MS received 20 February 1976, accepted 26 February 1976 G. ANLEZARK, C. PYCOCK and B. MELDRUM, Ergot alkaloids as dopamine agonists: comparison in two rodent models, European J. Pharmacol. 37 (1976) 295-302. A series of ergot alkaloids, together with the DA agonists apomorphine and piribedil, were tested for protec- tive effects against audiogenic seizures in an inbred strain of mice (DBA/2) and for induction of circling behaviour in mice with unilateral destruction of one nigrostriatal DA pathway. The order of potency against audiogenic sei- zures was apomorphine> ergocornine> bromocryptine > ergometrine> LSD> methysergide > piribedil while that observed in the rotating mouse model was apomorphine> ergometrine> ergocornine> brornocryptine > piribedil. LSD caused only weak circling behaviour even when administered in high doses (> 1 mg/kg). Methyser- gide was ineffective. Prior administration of the neuroleptic agent haloperidol blocked the effect of DA agonists and of ergot alkaloids in both animal models. The possible action of ergot alkaloids as DA agonists is discussed. Ergot alkaloids Audiogenic seizures Dopamine agonists Circling behaviour 1. Introduction gic synapses, in two rodent pharmacological models. The first model studied is 'audiogen- The pharmacology of the ergot alkaloids is ic' seizures in genetically susceptible mice. complex and not well understood. Peripheral- The severity of the seizure responses to audi- ly, they act on smooth muscle as 5-hydroxy- tory stimulation can be modified by a variety tryptamine (5-HT) antagonists (Goodman and of drugs believed to act on monoaminergic Gilman, 1971) and as a-adrenergic blockers transmission in the brain (Lehmann, 1970). -
Male Anorgasmia: from “No” to “Go!”
Male Anorgasmia: From “No” to “Go!” Alexander W. Pastuszak, MD, PhD Assistant Professor Center for Reproductive Medicine Division of Male Reproductive Medicine and Surgery Scott Department of Urology Baylor College of Medicine Disclosures • Endo – speaker, consultant, advisor • Boston Scientific / AMS – consultant • Woven Health – founder, CMO Objectives • Understand what delayed ejaculation (DE) and anorgasmia are • Review the anatomy and physiology relevant to these conditions • Review what is known about the causes of DE and anorgasmia • Discuss management of DE and anorgasmia Definitions Delayed Ejaculation (DE) / Anorgasmia • The persistent or recurrent delay, difficulty, or absence of orgasm after sufficient sexual stimulation that causes personal distress Intravaginal Ejaculatory Latency Time (IELT) • Normal (median) à 5.4 minutes (0.55-44.1 minutes) • DE à mean IELT + 2 SD = 25 minutes • Incidence à 2-11% • Depends in part on definition used J Sex Med. 2005; 2: 492. Int J Impot Res. 2012; 24: 131. Ejaculation • Separate event from erection! • Thus, can occur in the ABSENCE of erection! Periurethral muscle Sensory input - glans (S2-4) contraction Emission Vas deferens contraction Sympathetic input (T12-L1) SV, prostate contraction Bladder neck contraction Expulsion Bulbocavernosus / Somatic input (S1-3) spongiosus contraction Projectile ejaculation J Sex Med. 2011; 8 (Suppl 4): 310. Neurochemistry Sexual Response Areas of the Brain • Pons • Nucleus paragigantocellularis Neurochemicals • Norepinephrine, serotonin: • Inhibit libido, -
Hallucinogens: an Update
National Institute on Drug Abuse RESEARCH MONOGRAPH SERIES Hallucinogens: An Update 146 U.S. Department of Health and Human Services • Public Health Service • National Institutes of Health Hallucinogens: An Update Editors: Geraline C. Lin, Ph.D. National Institute on Drug Abuse Richard A. Glennon, Ph.D. Virginia Commonwealth University NIDA Research Monograph 146 1994 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 ACKNOWLEDGEMENT This monograph is based on the papers from a technical review on “Hallucinogens: An Update” held on July 13-14, 1992. The review meeting was sponsored by the National Institute on Drug Abuse. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. All other material in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. Citation of the source is appreciated. Opinions expressed in this volume are those of the authors and do not necessarily reflect the opinions or official policy of the National Institute on Drug Abuse or any other part of the U.S. Department of Health and Human Services. The U.S. Government does not endorse or favor any specific commercial product or company. -
Signs and Symptoms, Biology, and Awareness in This Section
Section 3: Facts about Methamphetamine Signs and Symptoms, Biology, and Awareness In This Section: Basic Facts about Methamphetamine, Source: This information was accessed in 2011 from www.methresources.gov which now redirects to the ONDCP website (2012). Signs and Symptoms of Methamphetamine, Source: This information was accessed in 2011 from NIDA InfoFacts: Methamphetamine which is no longer available on the NIDA website. Anatomy of a Meth User, www.kci.org Methamphetamine Abuse and Addiction, National Institute on Drug Abuse (NIDA) Research Report Series http://www.nida.nih.gov/PDF/RRMetham.pdf Methamphetamine and Teens, Source: This information was accessed in 2011 from www.theantidrug.com which now redirects to www.drugfree.org. Biology, Behavior and the Brain: Methamphetamine Addiction, Source: This information was accessed in 2011 from www.nationalmethcenter.org, a website which is now disabled. Links: Frontline: The Meth Epidemic, www.pbs.org/wgbh/pages/frontline/meth/ (video) NIDA Drug Facts: Methamphetamine, www.drugabuse.gov/drugs-abuse/methamphetamine NIDA Drug of Abuse: Methamphetamine, www.drugabuse.gov/publications/drugfacts/methamphetamine Source: National Institute on Drug Abuse (NIDA) Methamphetamine Use and Risk for HIV/AIDS, Centers for Disease Control (CDC) HIV/AIDS Fact Sheet www.cdc.gov/hiv/resources/factsheets/meth.htm Technical Support Document: Toxicology/Clandestine Drug Labs: Methamphetamine, California Office of Environmental Health Hazard Assessment, Volume 1, Number 8 http://oehha.ca.gov/public_info/pdf/TSD%20Methamphetamine%20Meth%20La bs%2010'8'03.pdf Basic Facts about Methamphetamine Methamphetamine is an addictive stimulant drug that strongly activates certain systems in the brain. Methamphetamine is closely related chemically to amphetamine, but the central nervous system effects of methamphetamine are greater. -
The Neurocircuitry of Illicit Psychostimulant Addiction: Acute and Chronic Effects in Humans
Substance Abuse and Rehabilitation Dovepress open access to scientific and medical research Open Access Full Text Article R E V IEW The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans Sara B Taylor1 Abstract: Illicit psychostimulant addiction remains a significant problem worldwide, despite Candace R Lewis1 decades of research into the neural underpinnings and various treatment approaches. The purpose M Foster Olive1,2 of this review is to provide a succinct overview of the neurocircuitry involved in drug addiction, as well as the acute and chronic effects of cocaine and amphetamines within this circuitry in 1Program in Behavioral Neuroscience, 2Interdisciplinary Graduate Program humans. Investigational pharmacological treatments for illicit psychostimulant addiction are in Neuroscience, Arizona State also reviewed. Our current knowledge base clearly demonstrates that illicit psychostimulants University, Tempe, AZ, USA produce lasting adaptive neural and behavioral changes that contribute to the progression and maintenance of addiction. However, attempts at generating pharmacological treatments for psychostimulant addiction have historically focused on intervening at the level of the acute effects of these drugs. The lack of approved pharmacological treatments for psychostimulant addiction highlights the need for new treatment strategies, especially those that prevent or ameliorate the adaptive neural, cognitive, and behavioral changes caused by chronic use of this class of illicit drugs. Keywords: -
Effects of Drugs Acting on Cerebral 5-Hydroxytryptamine Mechanisms on Dopamine-Dependent Turning Behaviour in Mice
Br. J. Pharmac. (1976), 56, 77-85 EFFECTS OF DRUGS ACTING ON CEREBRAL 5-HYDROXYTRYPTAMINE MECHANISMS ON DOPAMINE-DEPENDENT TURNING BEHAVIOUR IN MICE J.A. MILSON Department of Pharmacology, University of Bristol Medical School, Bristol BS8 1TD C.J. PYCOCK Department of Neurology, Institute of Psychiatry, Denmark Hill, London SE5 8AF I The effects of drugs acting on cerebral 5-hydroxytryptaminergic mechanisms on drug-induced turning behaviour in mice with unilateral destruction of nigro-striatal dopaminergic nerve terminals have been studied. 2 Administration of L-tryptophan (400 mg/kg) or 5-hydroxytryptophan (200 mg/kg) increased brain 5-hydroxytryptamine and decreased the turning induced by both apomorphine (2 mg/kg) and amphetamine (5 mg/kg). 3 Parachlorophenylalanine (3 x 500 mg/kg) decreased brain 5-hydroxytryptamine and increased both apomorphine and amphetamine-induced circling behaviour. 4 Varying the protein content of dietary intake significantly altered brain 5-hydroxytryptamine and tryptophan levels, spontaneous locomotor activity and amphetamine-induced circling behaviour in these mice. 5 Systemic administration of methysergide (0.5-4 mg/kg), lysergic acid diethylamide (0.025- 0.2 mg/kg), cyproheptadine (2.5-20 mg/kg) or clomipramine (0.6-20 mg/kg) produced no consistent effect on drug-induced turning behaviour. 6 The results suggest that circling behaviour due to striatal dopamine receptor stimulation is depressed by an elevation of brain 5-hydroxytryptamine and enhanced by a reduction in brain 5- hydroxytryptamine. 7 The possible physiological relationship between dopamine and 5-hydroxytryptamine neurones in the basal ganglia is discussed. Introduction Recent behavioural studies have stressed an inter- terminals of the intact side and cause the animal to relation between 5-hydroxytryptamine'and the cate- circle towards the damaged'side. -
Clozapine: Selective Labeling of Sites Resembling 5HT6 Serotonin Receptors May Reflect Psychoactive Profile
Clozapine: Selective Labeling of Sites Resembling 5HT6 Serotonin Receptors May Reflect Psychoactive Profile Charles E. Glatt, Adele M. Snowman, David R. Sibley, and Solomon H. Snyder Departments of Neuroscience, Pharmacology, and Molecular Sciences, and Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A., and Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, U.S.A. ABSTRACT Background: Clozapine, the classic atypical neuroleptic, receptors consistent with the drug's anticholinergic exerts therapeutic actions in schizophrenic patients un- actions. The drug competition profile of the second responsive to most neuroleptics. Clozapine interacts with site most closely resembles 5HT6 serotonin recep- numerous neurotransmitter receptors, and selective ac- tors, though serotonin itself displays low affinity. tions at novel subtypes of dopamine and serotonin re- [3H]Clozapine binding levels are similar in all brain ceptors have been proposed to explain clozapine's regions examined with no concentration in the cor- unique psychotropic effects. To identify sites with which pus striatum. clozapine preferentially interacts in a therapeutic setting, Conclusions: Besides muscarinic receptors, clozapine we have characterized clozapine binding to brain mem- primarily labels sites with properties resembling 5HT6 branes. serotonin receptors. If this is also the site with which Materials and Methods: [3H]Clozapine binding was clozapine principally interacts in intact human brain, it examined in rat brain membranes as well as cloned- may account for the unique beneficial actions of cloza- expressed 5-HT6 serotonin receptors. pine and other atypical neuroleptics, and provide a mo- Results: [3H]Clozapine binds with low nanomolar lecular target for developing new, safer, and more effec- affinity to two distinct sites. -
Methysergide Potentiates the Hyperactivity Produced by MDMA in Rats
Pharmacology Biochemistry & Behavior, Vol. 29, pp. 645-648. *>Pergamon Press plc, 1988. Printed in the U.S.A. 0091-3057/88 $3.00 + .00 BRIEF COMMUNICATION Methysergide Potentiates the Hyperactivity Produced by MDMA in Rats LISA H. GOLD AND GEORGE F. KOOB Department of Basic and Clinical Research, Research Institute of' Scripps Clinic 10666 North Torrey Pines Road, La Jolla, CA 92037 Received 21 July 1987 e GOLD, L. H. AND G. F. KOOB. Methysergide potentiates the hyperactivity produced by MDMA in rats. PHARMACOL BIOCHEM BEHAV 29(3) 645-648, 1988.--Although some substituted amphetamines, like MDA, produce a combination of sympathomimetic stimulation and perceptual alterations, the psychoactive qualities of MDMA are less distinctive. MDMA binds to serotonergic receptors and has been shown to potently deplete brain serotonin concentrations. Biochemi- cal and behavioral evidence suggests that MDMA may also act on the dopamine system. The present study explored the effects of blocking serotonin receptors on MDMA and amphetamine induced locomotor hyperactivity in rats. Locomotor activity was measured in photocell cages for 120 minutes following injection of methysergide (0. 2.5, 5, 10 mg/kg) or methysergide in combination with amphetamine (0.5 mg/kg) or MDMA (10 rog/kg). Methysergide, which had no effect on its own, significantly potentiated the locomotor hyperactivity produced by MDMA but not amphetamine. Thus, the intrinsic serotonergic agonist properties of MDMA may actually counteract the indirect sympathomimetic effects thought to be responsible for the locomotor hyperactivity MDMA produces. Methylenedioxymethamphetamine MDMA Methysergide Locomotor activity THERE has recently emerged a new category of recreational produces alterations in dopaminergic systems, the long term drugs called "designer drugs." This title refers to chemicals effects of MDMA (activity attributed to the + isomer) may that are prepared to produce desirable physical effects [16]. -
Interaction of Pergolide with Central Dopaminergic Receptors (Parkinsonism/Adenylate Cyclase) MENEK GOLDSTEIN*, ABRAHAM LIEBERMAN*, Jow Y
Proc. Natl. Acad. Sci. USA Vol. 77, No. 6, pp. 3725-3728, June 1980 Neurobiology Interaction of pergolide with central dopaminergic receptors (parkinsonism/adenylate cyclase) MENEK GOLDSTEIN*, ABRAHAM LIEBERMAN*, Jow Y. LEW*, TAKU ASANO*, MYRNA R. ROSENFELDt, AND MAYNARD H. MAKMANt *New York University Medical Center, Departments of Psychiatry and Neurology, 560 First Avenue, New York, New York 10016; and tAlbert Einstein College of Medicine, Departments of Biochemistry and Molecular Pharmacology, Bronx, New York 10461 Communicated by Michael Heidelberger, February 12,1980 ABSTRACT The activity of pergolide, an N-propylergoline MATERIALS AND METHODS derivative, has been tested for stimulation of central dopa- minergic receptors. Binding to dopamine receptors shows that Materials. [3H]Dopamine (8.4 Ci/mmol), [3H]Spiroperidol pergolide acts as an agonist with respect to these receptors. GTP ([3H]Spi) (23 Ci/mmol), N-n-[3H]propylnorapomorphine decreases the potencies of dopamine agonists and of pergolide, ([3H]NPA) (75 Ci/nmol) were purchased from New England but not of bromocriptine, to displace [3HJspiroperidol {43HSpi) Nuclear (1 Ci = 3.7 X 1010 becquerels). Pergolide was a gift from striatal membrane sites. The GTP-sensitive site labeled from Eli Lilly, and bromocriptine from Sandoz Pharmaceu- by [3HJSpi seems to be localized on intrastriatal dopamine re- tical. ceptors. The potency of dopamine agonists and of pergolide to Binding Assay. Preparation of bovine or rat membranes and displace [3HJSpi from striatal receptor sites is reduced in membranes exposed to higher temperatures. Pergolide, but not the ensuing binding assay were carried out as described (13). hitherto-tested dopaminergic ergots, stimulates do amine- For routine assay each tube contained 1.8 ml. -
Effects of Nitrous Oxide Exposure on Behavioral Changes in Mice
SCIENTIFIC ARTICLE Effects of nitrous oxide exposureon behavioral changesin mice Yiu K. Fung,PhD Michael R. Brown,DDS, MS Robert E. Sullivan, DDS,MSD Abstract This study was designedto examinethe effects of continuousexposure to low levels of nitrous oxide on several behavioral paradigmsand the occipital cortex cells of mice. Different groupsof mice wereexposed to air or two different levels of nitrous oxide (1000 ppmor 2000 ppm) 8 hr/day for eight consecutive days. The exposure to nitrous oxide was achieved by placing animalsin a specially designed,enclosed chamber. At the end of the exposureperiod, all mice weretested for motorcoordination, locomotoractivity, stereotypic behavior and anxiety level. Cellular examinationof the occipital cortex was conductedby counting both the larger neural cells and the smaller neuroglial cells in a specific region. Ourresults indicated that animals showedno deficit in motor coordination or anxiety level. Histological examinationindicated no significant difference in the numberof neural cells, neuroglial cells, or total cells countedin the control tissue, as comparedto the neuraltissue from mice exposedto nitrous oxide. Nitrous oxide-exposedmice showedreduced locomotor activity comparedto control animals; however, with the exception of one time period, this decreasewas not statistically significant. Animalsexposed to nitrous oxide showed a dose-dependentreduction in stereotypic behavior. Ourresults suggest that short-term exposureto trace levels of nitrous oxide might alter central dopaminergicneuronal activities in striatal and mesolimbicregions. Furtherresearch in this area is needed to provide moreinformation regardingthe potential effects of repeated exposureto low levels of nitrous oxide. (Pediatr Dent 15:93-98, 1993) Introduction Nitrous oxide is used in dentistry for its analgesic and dental operatory to be as high as 90,000 ppm27Other anxiolytic properties. -
The Effects of Stimulant Medication on the Social Behavior of Children with ADHD During Times of Play Robert, Jr
Louisiana State University LSU Digital Commons LSU Doctoral Dissertations Graduate School 2002 The effects of stimulant medication on the social behavior of children with ADHD during times of play Robert, Jr. H. LaRue Louisiana State University and Agricultural and Mechanical College, [email protected] Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_dissertations Part of the Psychology Commons Recommended Citation LaRue, Robert, Jr. H., "The effects of stimulant medication on the social behavior of children with ADHD during times of play" (2002). LSU Doctoral Dissertations. 2403. https://digitalcommons.lsu.edu/gradschool_dissertations/2403 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Doctoral Dissertations by an authorized graduate school editor of LSU Digital Commons. For more information, please [email protected]. THE EFFECTS OF STIMULANT MEDICATION ON THE SOCIAL BEHAVIOR OF CHILDREN WITH ADHD DURING TIMES OF PLAY A Dissertation Submitted to the Graduate Faculty of the Louisiana State University and Agricultural and Mechanical College In partial fulfillment of the Requirements for the degree of Doctor of Philosophy in The Department of Psychology by Robert H. LaRue Jr. B.A., Rutgers University, 1995 M.A., Louisiana State University, 2000 December 2002 TABLE OF CONTENTS LIST OF TABLES . iv ABSTRACT . v CHAPTER 1 INTRODUCTION . 1 Overview of the Literature. 1 The Developmental Significance of Play. 6 The Effects of Stimulants on Play and Related Social Behavior - Basic Research. 8 The Effects of Stimulants on Related Social Behavior in Rats and Non-Human Primates.