James Olds Biographical Memoir
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Brain Stimulation Reward
! Brain Stimulation Reward Peter Shizgal Groupe de recherche en neurobiologie comportementale and Department of Psychology Concordia University phone: +1 (514) 848-2424 ext 2191 fax: 1 (514) 848-2817 [email protected] http://csbn.concordia.ca/Faculty/Shizgal/!! Brain Stimulation Reward !Peter Shizgal Abstract In 1953, Olds and Milner discovered that rats would readily learn to work for electrical stimulation of certain brain sites. Their findings inspired a large body of research on the neural basis of reward, motivation, and learning. Unlike consummatory behaviors, which satiate as a result of ingestion of and contact with the goal object, performance for rewarding brain stimulation is remarkably stable and persistent. Pursuit of the stimulation is enhanced by different classes of dependence-inducing drugs, suggesting that common neural mechanisms underlie the rewarding effects of drugs and electrical brain stimulation. Indeed, dopamine- containing neurons in the midbrain are implicated in both phenomena. Major schools of thought that have addressed brain stimulation reward differ with regards to the roles played by hedonic experience and craving, although there is substantial overlap between the different viewpoints. A tradition that arose in the study of machine learning has been brought to bear on the role of dopamine neurons in reward-related learning in animals and on the phenomenon of intracranial self-stimulation. Neuroeconomic perspectives strive to integrate the processing of benefits, costs, and risks into an account of decision making grounded in brain circuitry. Adjudication of the differences between the various viewpoints and progress towards identifying the relevant neural circuitry has been hindered by the lack of specificity inherent in the use of electrical stimulation to study central nervous system function. -
Intraperitoneal Injections of a Dopamine-Receptor Blocking Agent
Neuroscience Letters, 1 (1975) 179--184 179 © Elsevier/North-Holland, Amsterdam- Printed in The Netherlands DIFFERENTIAL EFFECTS ON SELF.STIMULATION AND MOTOR BEHAVIOUR PRODUCED BY MICROINTRACRANIAL INJECTIONS OF A DOPAMINE-RECEPTOR BLOCKING AGENT F. MORA, A.M. SANGUINETTI, E.T. ROLLS and S.G. SHAW Department of Experimental Psychology, University of Oxford, Oxford (Great Britain) (Received September 8th, 1975) ( Accepted Se ~tember 8th, 1975) SUMMARY Intraperitoneal injections of a dopamine-receptor blocking agent, spiroperidol, equally and severely attenuated self-stimalation in two groups of rats which either performed the motor task of licking a tube or performed the more complex task of pressing a bar in order to obtain stimulation in the lateral hypothalamus. Unilateral microinjections of 9 ~g of spiroperidol into the nucleus accumbens attenuated self-stimulation without producing an appar- ent impairment of motor behaviour. The same injections into the corpus 3triatum produced an impairment of motor behaviour but self-stimulation was almost unaff~ted. The effect of spiroperidol on self-st£mulaticn can therefore be dissociated from the effect on motor behavlour. These results suggest that dopamine receptors are involved in self-stimulation independently of their role in motor behaviour. PhaL-macological and behavioural studi.es suggest that dopamine is involved in brain stimulation reward [ 2,5,16]. Self-stimulation of the lateral hypothal- amus and of other brain areas [ 11 ] is attenuated by the injection of pharma- cological agents which block dopamine receptors [ 10,11,13,15 ]. Since, how- ever, it is known that dopamine plays an important role in motor behaviour [6], the role of motor disturbance in the attenuation of self-stimulation produced by these pharmacological agents is not clear. -
Building a “Cross-Roads Discipline” at Mcgill University: a History of Early Experimental Psychology in Postwar Canada
BUILDING A “CROSS-ROADS DISCIPLINE” AT MCGILL UNIVERSITY: A HISTORY OF EARLY EXPERIMENTAL PSYCHOLOGY IN POSTWAR CANADA ERIC OOSENBRUG A dissertation submitted to the Faculty of Graduate Studies in partial fulfillment of the requirements for the degree of Doctor of Philosophy Graduate Program in Psychology. Graduate Program in Psychology York University Toronto, Ontario October 2020 © Eric Oosenbrug, 2020 Abstract This dissertation presents an account of the development of psychology at McGill University from the late nineteenth century through to the early 1960s. The department of psychology at McGill represents an alternative to the traditional American-centered narrative of the cognitive revolution and later emergence of the neurosciences. In the years following World War II, a series of psychological experiments established McGill as among the foremost departments of psychology in North America. This thesis is an institutional history that reconstructs the origins, evolution, and dramatic rise of McGill as a major center for psychological research. The experiments conducted in the early 1950s, in the areas of sensory restriction, motivation, and pain psychology, were transformative in their scope and reach. Central to this story is Donald O. Hebb, author of The Organization of Behavior (1949), who arrived at McGill in 1947 to find the charred remains of a department. I argue that the kind of psychology Hebb established at McGill was different from most departments in North America; this is developed through a number of interwoven storylines focused on the understanding of a particular character of McGill psychology - a distinctive “psychological style” - and its broader historical importance for Canadian psychology, for North American psychology, and for psychology across the globe. -
The Role of Dopamine in Intracranial Self-Stimulation of the Ventral Tegmental Area
The Journal of Neuroscience, December 1987, 7(12): 38883896 The Role of Dopamine in Intracranial Self-Stimulation of the Ventral Tegmental Area H. C. Fibiger, F. G. LePiane, A. Jakubovic, and A. G. Phillips Division of Neurological Sciences, Department of Psychiatry and Department of Psychology, The University of British Columbia, Vancouver, B.C. V6T 2A1, Canada The role of dopaminergic (DA) neurons in brain stimulation Intracranial self-stimulation (1’3) can be obtained from nu- reward produced by electrical stimulation of the ventral teg- meroussites in the central nervoussystem (Phillips, 1984).There mental area (VTA) was investigated in the rat. In the first is considerableevidence that dopaminergic (DA) neurons are experiment, extensive 6-hydroxydopamine lesions of the as- among the neural substratesthat mediate the reinforcing prop- cending fibers of the mesotelencephalic DA projections re- erties of ICS obtained from at least some of these sites. For sulted in significant changes in intracranial self-stimulation example, the robust ICS obtained from electrodesin the ventral (ICS) rate-current intensity functions when the lesion was tegmental area (VTA), a region rich in DA perikarya, is greatly ipsilateral to the stimulating electrode. Similar contralateral reduced after selective lesions of the ascendingprojections of lesions had no effect on these functions, thus ruling out these neurons (Phillips and Fibiger. 1978). Similarly, ICS ob- lesion-induced performance deficits as being responsible tained from electrodesin the lateral hypothalamus is much re- for the decreases in ICS rates across the wide range of duced by lesionsof the VTA (Koob et al., 1978). In the above current intensities that occurred after the ipsilateral lesions. -
Malanga Lab Reveals the Basis of the “Buzz” New Evidence For
UNC Bowles Center for Alcohol Studies Non-Profit Organization CB# 7178, Thurston-Bowles Building US Postage University of North Carolina at Chapel Hill PAID Chapel Hill, North Carolina 27599-7178 Permit No. 177 Chapel Hill, NC 27599-1800 Center Line Bowles Center for Alcohol Studies School of Medicine, University of North Carolina at Chapel Hill Our mission is to conduct, coordinate, and promote basic and clinical research on the causes, prevention, and treatment of alcoholism and alcoholic disease. Volume 20, Number 3, September 2009 Malanga Lab Reveals the Basis of the “Buzz” Many people drink alcohol for the receive electrical stimulation of the necessary to for animals to maintain “buzz”—those feelings of relaxation, ventral tegmental area, a component of responding to obtain intracranial geniality, and heightened interest that the mesolimbic system and part of the stimulation. Reductions in brain can accompany drinking in moderation. brain’s reward circuitry. It is thought that stimulation reward thresholds reflect In short, mild intoxication is pleasurable intracranial self-stimulation activates the pleasurable activation of the mesolimbic New Evidence for Metabotropic Glutamate Receptors and rewarding. How important is that brain’s reward circuitry to produce reward system, and the lowering of the As Targets for Alcoholism Therapy “buzz” in the development of feelings of pleasure and euphoria in the threshold for brain stimulation reward alcoholism? Is the “buzz” more same way as drugs of abuse. Animals is a means of quantifying the rewarding All drugs of abuse produce distinct interoceptive/subjective Center for Alcohol Studies and the pleasurable to some people than to work in order to have drugs of abuse and pleasurable effects of drugs in effects that are perceived by the individual and can be Department of Psychiatry, and others? Do inter-individual animals. -
Conquering the Mind
AMERICA’S NEXT FRONTIER: CONQUERING THE MIND AC INST M IT O U T B T O E P SYMPOSIUM REPORT F O S G E R I September 24, 2014 P D O U LICY ST Sponsored by: Potomac Institute for Policy Studies The sponsors and publisher gratefully acknowledge participants’ contributions included in this event report. Please note that the transcript has been edited for publication. The sponsor and publisher cannot assume responsibility for the validity of all materials or the consequences of their use; the view and opinions expressed do not necessarily reflect those of the Potomac Institute for Policy Studies or Potomac Institute Press. For further information about this symposium series or reports, please contact the Director of the Center for Neurotechnology Studies, Jennifer Buss, Ph.D. at: [email protected]. Copyright © 2015, by Potomac Institute Press Potomac Institute for Policy Studies 901 N. Stuart St, Suite 1200 Arlington, VA, 22203 www.potomacinstitute.org Telephone: 703.525.0770; Fax: 703.525.0299 Email: [email protected] TABLE OF CONTENTS Symposium Agenda: September 24, 2014 . 5 Executive Summary . 7 Findings, Conclusions, and Recommendations . 8 Theme #1: Expanding the Brain Initiative into a National Neurotechnology Initiative . 8 Theme #2: Building a National Neurotechnology Industry . 10 Theme #3: Coordinating a Neurotechnology Initiative Across Federal Agencies . 11 Event Transcript . 14 Jennifer Buss . 14 Opening Remarks Mike Swetnam . 14 Introduction Congressman Chaka Fattah . 16 Opening Remarks Panel . 18 Panel Summary . 18 James L. Olds . 18 The “How’s and Why’s” of Brain Mapping Amy Kruse . 21 Developing Neurotechnology for the Brain Peter Littlewood . -
Review Brain Reward Circuitry
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Neuron, Vol. 36, 229–240, October 10, 2002, Copyright 2002 by Cell Press Brain Reward Circuitry: Review Insights from Unsensed Incentives Roy A. Wise1 as to the trigger zones at which addictive drugs initiate Behavioral Neuroscience Branch their habit-forming actions. The second discusses pos- Intramural Research Program sible explanations for the fact that drug reward and brain National Institute on Drug Abuse stimulation reward establish seemingly more compul- National Institutes of Health sive habits than do the natural pleasures of life. The final Bethesda, Maryland 20892 section illustrates—again, by contrasting sensed and unsensed incentives—the fuzziness of the distinction between the “receipt” of reward and the prediction of The natural incentives that shape behavior reach the reward. central circuitry of motivation trans-synaptically, via the five senses, whereas the laboratory rewards of Anatomy of Drug Reward intracranial stimulation or drug injections activate re- While there is much to learn about which dopamine ward circuitry directly, bypassing peripheral sensory neurons play roles in incentive motivation and reinforce- pathways. The unsensed incentives of brain stimula- ment and there is much more to learn about the afferents tion and intracranial drug injections thus give us tools to and the efferents from those dopamine neurons, a to identify reward circuit elements within the associa- good deal is known about the brain structures and re- tional portions of the CNS. Such studies have impli- ceptor subtypes at which addictive drugs trigger their cated the mesolimbic dopamine system and several habit-forming actions. -
Drug Abuse, Dopamine, and the Brain's Reward System
RESEARCHUPDATE BUTLER CENTER FOR RESEARCH SEPTEMBER 2015 Research Update is published by the Butler Center for Research to share significant scientific findings from the field of addiction treatment research. Drug Abuse, Dopamine, and the THE HAZELDEN BETTY FORD FOUNDATION EXPERIENCE Treatment at each of the Hazelden Betty Ford Foundation Brain’s Reward System sites is constantly guided and improved by scientific Why do people continue to use alcohol and other drugs chronically even after experiencing innovation. As a result, our treatment plans incorporate serious medical, social, legal, or financial consequences? This is a question that has interested pharmacological treatments with traditional counseling professionals in a wide variety of addiction-related fields for many years. Advances in sessions for patients with high-risk dependence behaviors. neuroscience and biology have allowed scientists to better understand the physical roots of Our recently launched COR-12TM program offers opioid- substance use and dependence, which has led to the contemporary disease model of addiction. dependent patients Twelve Step-based treatment By studying and understanding the biological characteristics of substance dependence, paired with cognitive-behavioral therapy, motivational scientists and physicians are able to develop medical and pharmacological treatments that can interviewing, and opioid agonist and antagonist significantly improve recovery outcomes. medications that help control cravings by gradually reducing the amount of dopamine in the system. Basics of Brain Function and Neurotransmitters In order to carry out all of its necessary functions, from making sure your lungs are breathing QUESTIONS AND CONTROVERSIES to working out a calculus algorithm, the brain uses a complex communication system made up of tree-like cells called neurons. -
Craving, Desire, and Addiction, As These Are Among the Most Pressing Causes of Human Suffering
MIND & LIFE INSTITUTE MIND AND LIFE XXVII Craving, Desire, and Addiction DHARAMSALA, HIMACHAL PRADESH, INDIA OCTOBER 28–NOVEMBER 1, 2013 OVERVIEW The mission of the Mind & Life Institute is to alleviate suffering and to promote human flourishing. We seek to achieve these broad goals in specific ways, especially by bringing together scientists, contemplatives, and scholars in order to deepen our insights into the causes of suffering and the means by which we can support human life at its most holistic. Desire is a natural part of life that provides the motivating force for our achieve- ments. Our highest aspirations are animated by desire. Yet, when desire becomes obsession or craving, we cross over into the territory of suffering. What before was an aid to accomplishment can devolve into a source of personal anguish and social violence. Behavioral and substance addictions are the expression of desires that have become obsessions. The harmful patterns of addiction take a profound toll on both the individual and society. Addiction to alcohol, tobacco, and illicit drugs, for example, is estimated to cost the United States $600 billion per year. The Mind & Life Institute has chosen to focus its attention on craving, desire, and addiction, as these are among the most pressing causes of human suffering. By bringing contemplative practitioners and scholars from Buddhist and Chris- tian traditions together with a broad array of scientific researchers in the fields of desire and addiction, we hope new understandings will arise that may ultimately lead to improved treatment of the root causes of craving and its many manifesta- tions. -
The Mesolimbic Dopamine Reward Circuit in Depression Eric J
The Mesolimbic Dopamine Reward Circuit in Depression Eric J. Nestler and William A. Carlezon, Jr. The neural circuitry that mediates mood under normal and abnormal conditions remains incompletely understood. Most attention in the field has focused on hippocampal and frontal cortical regions for their role in depression and antidepressant action. While these regions no doubt play important roles in these phenomena, there is compelling evidence that other brain regions are also involved. Here we focus on the potential role of the nucleus accumbens (NAc; ventral striatum) and its dopaminergic input from the ventral tegmental area (VTA), which form the mesolimbic dopamine system, in depression. The mesolimbic dopamine system is most often associated with the rewarding effects of food, sex, and drugs of abuse. Given the prominence of anhedonia, reduced motivation, and decreased energy level in most individuals with depression, we propose that the NAc and VTA contribute importantly to the pathophysiology and symptomatology of depression and may even be involved in its etiology. We review recent studies showing that manipulations of key proteins (e.g. CREB, dynorphin, BDNF, MCH, or Clock) within the VTA-NAc circuit of rodents produce unique behavioral phenotypes, some of which are directly relevant to depression. Studies of these and other proteins in the mesolimbic dopamine system have established novel approaches to modeling key symptoms of depression in animals, and could enable the development of antidepressant medications with fundamentally new mechanisms of action. Key Words: Ventral striatum, nucleus accumbens, ventral tegmen- also raises the possibility that different subtypes of depression tal area, CREB, dynorphin, BDNF, MCH, orexin, melanocortin, Clock, may be mediated by pathology localized to different brain areas, NPAS2 which might be responsive to very different types of treatments. -
The Neurobiology of Nicotine Addiction: Bridging the Gap from Molecules to Behaviour
REVIEWS THE NEUROBIOLOGY OF NICOTINE ADDICTION: BRIDGING THE GAP FROM MOLECULES TO BEHAVIOUR Steven R. Laviolette and Derek van der Kooy Nicotine, the primary psychoactive component of tobacco smoke, produces diverse neurophysiological, motivational and behavioural effects through several brain regions and neurochemical pathways. Recent research in the fields of behavioural pharmacology, genetics and electrophysiology is providing an increasingly integrated picture of how the brain processes the motivational effects of nicotine. The emerging characterization of separate dopamine- and GABA (γ-aminobutyric acid)-dependent neural systems within the ventral tegmental area (VTA), which can mediate the acute aversive and rewarding psychological effects of nicotine, is providing new insights into how functional interactions between these systems might determine vulnerability to nicotine use. The addictive nature of nicotine remains a global health neurotransmitter systems, the potential roles of specific epidemic. Over three million smoking-related deaths neuronal nicotinic acetylcholine receptor (nAChR) are reported annually, worldwide. In the Western world, subtypes and specific neuroanatomical regions that illness related to smoking is believed to be the cause of have been implicated in mediating the addictive prop- 20% of all deaths, making nicotine addiction the single erties of nicotine. In particular, we will review the con- largest cause of preventable mortality1,2.Despite these siderable body of evidence that implicates dopamine grim statistics, tobacco use is increasing in many devel- (DA) and non-DA neuronal substrates in the ventral oping countries3,with smoking-related mortalities tegmental area (VTA) as crucial for the rewarding and predicted to exceed 10 million per year over the coming aversive motivational properties of nicotine. -
Dopamine D3 Receptor Antagonism Inhibits Cocaine-Seeking and Cocaine-Enhanced Brain Reward in Rats
The Journal of Neuroscience, November 1, 2002, 22(21):9595–9603 Dopamine D3 Receptor Antagonism Inhibits Cocaine-Seeking and Cocaine-Enhanced Brain Reward in Rats Stanislav R. Vorel,1,2 Charles R. Ashby Jr,4 Mousumi Paul,5 Xinhe Liu,3 Robert Hayes,2 Jim J. Hagan,6 Derek N. Middlemiss,6 Geoffrey Stemp,6 and Eliot L. Gardner1,2,3 1Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, Departments of 2Neuroscience and 3Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York 10461, 4Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Saint John’s University, Jamaica, New York 11439, 5Eon Laboratories, Laurelton, New York 11413, and 6Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, Essex CM19 5AW, United Kingdom The dopamine D3 receptor is preferentially localized to the (2) dose-dependently attenuate cocaine-induced conditioned mesocorticolimbic dopaminergic system and has been hypoth- place preference, and (3) dose-dependently attenuate cocaine- esized to play a role in cocaine addiction. To study the involve- triggered reinstatement of cocaine seeking behavior. Thus, D3 ment of the D3 receptor in brain mechanisms and behaviors receptor blockade attenuates both the rewarding effects of commonly assumed to be involved in the addicting properties cocaine and cocaine-induced drug-seeking behavior. These of cocaine, the potent and selective D3 receptor antagonist data suggest an important role for D3 receptors in mediating the trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl] addictive properties of cocaine and suggest that blockade of cyclohexyl]-4-quinolininecarboxamide (SB-277011-A) was ad- dopamine D3 receptors may constitute a new and useful target ministered to laboratory rats, and the following measures were for prospective pharmacotherapies for cocaine addiction.