Psychopharmacology - 4th Generation of Progress


Psychopharmacology: The Fourth Generation of Progress"This volume, Psychopharmacology: The Fourth Generation of Progress, seeks to redefine the scientific field of neuropsychopharmacology for its parent organization, The American College of Neuropsychopharmacology.  The field's definition has been constructed from the two interrelated bodies of work that comprise the major working arms of the College: the clinical investigation of psychiatry and neurological disorders in terms of their biologically defined mechanisms of pathogenesis, treatment and prevention; and the preclinical foundations of neuropsychopharmacology in terms of the essential signaling mechanisms by which neurons interact to perform the behavioral level operations of the brain and mental activity.  In these parallel tracks of effort, drugs are a tool to dissect the chemical signaling systems of the brain, as well as a means to restore functions disrupted by brain diseases.  The better the characterization of the clinical signaling systems, the more insightful will be the analyses of the drugs in their therapeutic assessment.      

A slight departure of this book from its predecessor volume is the attempt to provide a more comprehensive overview of the clinical and preclinical arms of the field.  Here the approach is designed first to provide new scholars with overviews of preclinical and clinical psychopharmacology, and then more detailed coverage to understand the methods by which data in each of these arms are assessed in research.  The introductory sections provide a basis for the detailed coverage of the enormous amounts of progress that have been achieved since the previous volume. Finally, the coverage builds upon these foundations with assessments of the most recent cross-cutting issues.  There is internationally extensive cross-referencing between clinical and preclinical subjects.  The text is designed to allow experts in both spheres to find the latest assessments of progress, while also permitting the less experienced readers to increase their appreciation of the work underway. 

By providing a road map to the linkages between the major topics of today's research, the editors and authors hope to illuminate critically the most exciting discoveries, as well as to indicate the important gaps that need attention, while allowing room for the unexpected discoveries that will almost certainly emerge."         

Floyd E. Bloom, MD
David J. Kupfer, MD

Raven Press, New York, New York, 1995

(Adapted from the Preface of the Psychopharmacology: the Fourth Generation of Progress)



Table of Contents



Introduction to Preclinical Neuropsychopharmacology: Floyd E. Bloom

Critical Analysis of Methods

Basic Concepts and Techniques of Molecular Genetics: Samuel H. Barondes

Cytology and Circuitry: Stanley J. Watson, Jr. and William E. Cullinan

revised A Critical Analysis of Neurochemical Methods for Monitoring Transmitter Dynamics in the Brain: Janet M. Finlay and Gwenn S. Smith

Electrophysiology: Gary S. Aston-Jones and George R. Siggins

Behavioral Techniques in Preclinical Neuropsychopharmacology Research: James E. Barrett and Klaus A. Miczek

Transmitter Systems 

Amino Acids

Excitatory Amino Acid Neurotransmission: Carl W. Cotman, Jennifer S. Kahle, Stephan E. Miller, Jolanta Ulas, and Richard J. Bridges

GABA and Glycine: Steven M. Paul


revised Neuronal Nicotinic Acetylcholine Receptors: Novel Targets for CNS Therapeutics: Michael W. Decker, James P. Sullivan, Stephen P. Arneric, and Michael Williams

Molecular Biology, Pharmacology, and Brain Distribution of Subtypes of the Muscarinic Receptor: Frederick J. Ehlert, William R. Roeske, and Henry I. Yamamura

Cholinergic Transduction: Elliott Richelson

Structure and Function of Cholinergic Pathways in the Cerebral Cortex, Limbic System, Basal Ganglia, and Thalamus of the Human Brain: Marek-Marsel Mesulam

Functional Heterogeneity of Central Cholinergic Systems: Peter B. Reiner and H. Christian Fibiger


Molecular Biology of the Dopamine Receptor Subtypes: Olivier Civelli

Electrophysiological Properties of Midbrain Dopamine Neurons: Anthony A. Grace and Benjamin S. Bunney

revised The Dopamine Transporter: Potential Involvement in Neuropsychiatric Disorders: Michael J. Bannon, Paola Sacchetti and James G. Granneman

Long-and Short- Term Regulation of Tyrosine Hydroxylase: Menek Goldstein

Colocalization in Dopamine Neurons: Ariel Y. Deutch and Andrew J. Bean

Dopamine Receptor Expression in the Central Nervous System: Alfred Mansour and Stanley J. Watson, Jr.

Dopamine Autoreceptor Signal Transduction and Regulation: Louis A. Chiodo, Arthur S. Freeman, and Benjamin S. Bunney

Biochemical Pharmacology of Midbrain Dopamine Neurons: Robert H. Roth and John D. Elsworth

revised Dopaminergic Neuronal Systems in the Hypothalamus: Kenneth E. Moore and Keith J. Lookingland

revised Electron Microscopy of Central Dopamine Systems: Virginia M. Pickel and Susan R. Sesack

Development of Mesencephalic Dopamine Neurons in the Nonhuman Primate: Relationship to Survival and Growth Following Neural Transplantation: John R Sladek, Jr., Barbara Blanchard, T. J. Collier, John D Elsworth, Jane R. Taylor, Robert H. Roth, and D. Eugene Redmond, Jr.

Mesocorticolimbic Dopaminergic Neurons: Functional and Regulatory Roles: Michel Le Moal

Dopamine Receptor Transcript Localization in Human Brain: James H. Meador-Woodruff

Dopamine Receptors: Clinical Correlates: Philip Seeman

revised Signal Transduction Pathways for Catecholamine Receptors: Ronald S. Duman and Eric J. Nestler

Norepinephrine and Serotonin Transporters: Molecular Targets of Antidepressant Drugs: Eric L. Barker and Randy D. Blakely

Pharmacology and Physiology of Central Noradrenergic Systems: Stephen L. Foote and Gary S. Aston-Jones

Coexisting Neurotransmitters in Central Noradrenergic Neurons: Philip V. Holmes and Jacqueline N. Crawley

Modification of Central Catecholaminergic Systems by Stress and Injury: Functional Significance and Clinical Implications: Elizabeth D. Abercrombie and Michael J. Zigmond

revised Central Norepinephrine Neurons and Behavior: Trevor W. Robbins and Barry J. Everitt

The Noradrenergic Receptor Subtypes: Magdalena Wozniak, Nicole L. Schramm and Lee E. Limbird

Physiological and Anatomical Determinants of Locus Coeruleus Discharge: Behavior and Clinical Implications: Rita J. Valentino and Gary S. Aston-Jones

Noradrenergic Neural Substrates for Anxiety and Fear: Clinical Associations Based on Preclinical Research: Dennis S. Charney, J. Douglas Bremner, and D. Eugene Redmond, Jr.

Histamine: Jean-Charles Schwartz, Jean-Michel Arrang, and Monique Garbarg

Molecular Biology of Serotonin Receptors: A Basis for Understanding and Addressing Brain Function: Jean Chen Shih, Kevin J.-S. Chen, and Timothy K. Gallaher

Serotonin Receptor Subtypes and Ligands: Richard A. Glennon, Malgorzata Dukat, and Richard B. Westkaemper

Gene Targeting Approaches to Serotonin Receptors: Laurence Tecott, M.D., Ph. D.

Serotonin Receptors: Signal Transduction Pathways: Elaine Sanders-Bush and Herv Canton

Anatomy, Cell Biology, and Maturation of the Serotonergic System: Neurotrophic Implications for the Actions of Psychotropic Drugs: Efrain C. Azmitia

Electrophysiology of Serotonin Receptor Subtypes and Signal Transduction Pathways: George K. Aghajanian

Serotonin and Behavior: A General Hypothesis: Barry L. Jacobs and Casimir A. Fornal

revised Indoleamines: The Role of Serotonin in Clinical Disorders: George R. Heninger

Monoamine Oxidase: Basic and Clinical Perspectives: D.P. Holschneider, M.D., J.C. Shih, Ph.D.


revised General Overview of Neuropeptides: Tomas Hakfelt, Zhi-Qing David Xu, Christian Broberger, Tiejun Sten Shi, and Xu Zhang

Thyrotropin-Releasing Hormone: Focus on Basic Neurobiology: George A. Mason, James C. Garbutt, and Arthur J. Prange, Jr.

Corticotropin-Releasing Factor: Physiology, Pharmacology, and Role in Central Nervous System and Immune Disorders: Errol B. De Souza and Dimitri Goriadis

Neuropharmacology of Endogenous Opioid Peptides: John J. Wagner and Charles I. Chavkin

Vasopressin and Oxytocin in the Central Nervous System: Linda Rinaman, Thomas G. Sherman, and Edward M. Stricker

Neuropeptide Y and Related Peptides: Claes Wahlestedt and Markus Heilig

Somatostatin in the Central Nervous System: David R. Rubinow, Candace L. Davis, and Robert M. Post

Galanin: A Neuropeptide with Important Central Nervous System Actions: Tamas Bartfai

revised The Neurobiology of Neurotensin: Garth Bissette and Charles B. Nemeroff

Cholecystokinin: Margery C. Beinfeld

Vasoactive Intestinal Peptide in Central Nervous: Douglas E. Brenneman, Joanna M. Hill, and Illana Gozes

Luteinzing Hormone-Releasing Hormone Neuronal: Serge Rivest and Leonello Cusan

New Transmitters

Arachidonic Acid: Daniele Piomelli

Nitric Oxide and Related Substance as Neural Messengers: Solomon H. Snyder and Ted M. Dawson

Neuronal Growth and Differentiation Factors and Synaptic Placticity: Paul H. Patterson

Proto-Oncogenes: Beyond Second Messengers: James I. Morgan and Thomas E. Curran

revised Purinergic Mechanisms in Nervous System Function and Disease States: Michael F. Jarvis and Michael Williams

Integrative Concepts

Brain Energy Metabolism: An Integrated Cellular Perspective: Pierre J. Magistretti, Luc Pellerin, and Jean-Luc Martin

Molecular and Cellular Mechanisms of Brain Development: David A. Morilak, Matthew H. Porteus, and Roland D. Ciaranello

The Development of Brain and Behavior: Thomas R. Insel

revised Intracellular Messenger Pathways as Mediators of Neural Plasticity: Eric J. Nestler and Ronald S. Duman

revised Neuroendocrine ions: Bruce S. McEwen

Interactions Between the Nervous System and the Immune System: Implications for Psychopharmacology: Adrian J. Dunn

Adaptive Processes Regulating Tolerance to Behavioral Effects of Drugs: Alice M. Young and Andrew J. Goudie

The Psychopharmacology of Sexual Behavior: James G. Pfaus and Barry J. Everitt

revised Animal Models of Drug Addiction: George F. Koob

Stress: Huda A. Akil and M. Inés Morano

Circadian Rhythms: C.S. Colwell

Processes Underlying Sleep Regulation: Alexander A. Borbely, Peter Achermann, Beat Geering, and Irene Tobler

Animal Models of Psychiatric Disorders: Mark A. Geyer and Athina Markou

revised Genetic Stategies in Preclinical Subtsance Abuse Research: Kaitlin E. Browman, John Crabbe, and Ting-Kai Li

Molecular Analysis of the Single Cell: Importance: James Eberwine, Peter Crino, Steve Arnold, John Trojanowski, and Scott Hemby

Astroglial Pharmacology: Elisabeth Hansson, Thorleif Thorlin, Mattias Linde, Fredrik Blomstrand, Peter S. Eriksson, Ulrika Johansson, Siamak Khatibi, Michael Nilsson, Torsten Olsson, David Auberg and Lars Ronnback

new Molecular Neurobiology of Development: Flora M. Vaccarino and James F. Leckman



revised Introduction to Clinical Neuropsychopharmacology: David J. Kupfer

Critical Analysis of Methods

The DSM-IV Classification and Psychopharmacology: Allen Frances, Avram H. Mack, Ruth Ross, and Michael B. First

Clinical Study Design Critical Issues: Donald S. Robinson, M.D. and Nina R. Schooler, Ph.D.

Short-and Long-Term Psychopharmacological Treatment Strategies: Ira D. Glick, David L. Braff, and David S. Janowsky

Pharmacokinetics and Pharmacodynamics: David J. Greenblatt, Jerold S. Harmatz, Lisa L. von Moltke, and Richard I. Shader

Cytochrome Enzymes and Psychopharmacology: Sheldon H. Preskorn, M.D. and Anne T. Harvey, Ph.D.

Methodological Issues in the Neuropathology of Mental Illness: Joel E. Kleinman, Thomas M. Hyde, and Mary M. Herman

Positron and Single Photon Emission Tomography: Principles and Applications in Psychopharmacology: Robert T. Malison, Marc Laruelle, and Robert B. Innis

revised In Vivo Structural Brain Assessment: Kelvin O. Lim, Margaret Rosenbloom, and Adolf Pfefferbaum

Methodological Issues in Event-Related Brain Potential and Magnetic Field Studies: Walton T. Roth, Judith M. Ford, Adolf Pfefferbaum, and Thomas R. Elbert

new Psychiatric Genetics: Joel Gelernter and David Goldman

Psychiatric Disorders

Mood Disorders

Recent Studies on Norepinephrine Systems in Mood Disorders: Alan F. Schatzberg and Joseph J. Schildkraut

revised Dopaminergic Mechanisms in Depression and Mania: Paul Willner

The Serotonin Hypothesis of Major Depression: Michael Maes and Herbert Y. Meltzer

revised The Role of Acetylcholine Mechanisms in Affective Disorders: David S. Janowsky and David H. Overstreet

Neuroendocrinology of Mood Disorders: Florian Holsboer

Neuropeptide Alterations in Mood Disorders: Paul M. Plotsky, Michael J. Owens, and Charles B. Nemeroff

Psychoneuroimmunology of Depression: Michael Irwin

Biological Rhythms in Mood Disorders: Anna Wirz-Justice

Brain Imaging in Mood Disorders: Godfrey D. Pearlson, MD and Thomas E. Schlaepfer, MD

revised Mood Disorders Linked to the Reproductive Cycle in Women: Barbara L. Parry and Patricia Haynes

Selective Serotonin Reuptake Inhibitors in the Acute Treatment of Depression: Stuart A. Montgomery

Standard Antidepressant Pharmacotherapy for the Acute Treatment of Mood Disorders: Michael J. Burke, M.D., Ph.D. and Sheldon H. Preskorn, M.D.

Long-Term Treatment of Mood Disorders: Robert F. Prien and James H. Kocsis

Treatment-Resistant Depression: Michael E. Thase and A. John Rush

revised Lithium and the Anticonvulsants in Bipolar Disorder: Joseph R. Calabrese and Charles Bowden

Psychosocial Predictors of Outcome in Depression: Robert M. A. Hirschfeld

Electroconvulsive Therapy: Harold A. Sackeim, D. P. Devanand, and Mitchell S. Nobler

Novel Pharmacological Approaches to the Treatment of Depression: Denis L. Murphy, Philip B. Mitchell, and William Z. Potter

The Neurobiology of Treatment-Resistant Mood Disorders: Robert M. Post and Susan R. B. Weiss


Neurodevelopmental Perspectives on Schizophrenia: Daniel R. Weinberger

Physiological Indicators of the Schizophrenia Phenotype: Robert Freedman, Randal G. Ross, and Lawrence E. Adler

Functional Brain-Imaging Studies in Schizophrenia: Raquel E. Gur

New Developments in Dopamine and Schizophrenia: René S. Kahn and Kenneth L. Davis

Schizophrenia and Glutamate: An Update: Blynn Garland Bunney, Ph.D. William E. Bunney, Jr., M.D. and Arvid Carlsson

The Role of Serotonin in Schizophrenia: Herbert Y. Meltzer, M.D., Ph.D. and Bryan Roth, M.D.

The Effects of Neuroleptics on Plasma Homovanillic Acid: Arnold J. Friedhoff and Raul R. Silva

Neurophysiological and Psychophysiological Approaches to Schizophrenia: Keith H. Nuechterlein, Ph.D.

Neurocognitive Functioning in Patients with Schizophrenia: An Overview: Terry E. Goldberg and James M. Gold

Acute Treatment of Schizophrenia: William C. Wirshing, M.D., Donna Ames-Wirshing, M.D., Stephen R. Marder, M.D., and Theodore Van Putten, M.D.

revised Maintenance Drug Treatment for Schizophrenia: John G. Csernansky

Atypical Antipsychotic Drugs: Herbert Y. Meltzer

Anxiety Disorders

Neuroimaging Studies of Human Anxiety Disorders: Cutting Paths of Knowledge through the Field of Neurotic Phenomena: Lewis R. Baxter, Jr.

Anxiety and Serotonin1A Receptor: Jeremy D. Coplan, Susan I. Wolk, and Donald F. Klein

Pharmacological Challenges in Anxiety Disorders: Lawrence H. Price, Andrew W. Goddard, Linda C. Barr, and Wayne K. Goodman

Environmental Factors in the Etiology of Anxiety: Karrie J. Craig, Kelly J. Brown, and Andrew Baum

The Pharmacotherapy of Acute Anxiety: A Mini-Update: Richard I. Shader and David J. Greenblatt

Issues Long-Term Treatment of Anxiety Disorders: Edward Schweizer, Karl Rickels, and Eberhard H. Uhlenhuth

Post-Traumatic Stress Disorder : Matthew A. Friedman

newPharmacotherapy of Panic Disorder: Smit S. Sinha, Justine Kent, and Jack M. Gorman

Geriatric Disorders

Towards an Understanding of the Genetics of Alzheimer's Disease: Corrine L. Lendon and Alison M. Goate

Amyloidogenesis in Alzheimer's Disease and Animal Models: Sangram S. Sisodia, and Donald L. Price

Neuropsychological Assessment of Patients with Alzheimer's Disease: Richard C. Mohs

Biological Markers in Alzheimer's Disease: Trey Sunderland, Susan E. Molchan, and George S. Zubenko

Anatomic and Functional Brain Imaging in Alzheimer's Disease: Stanley I. Rapoport

Experimental Therapeutics: Deborah B. Marin and Kenneth L. Davis

Alzheimer's Disease: Treatment of Noncognitive Behavioral Abnormalities: Murray A. Raskind

Late-Onset Schizophrenia and Other Related Psychoses: Dilip V. Jeste, Jane S. Paulsen, and M. Jackuelyn Harris

Cognitive Impairment in Geriatric Schizophrenic Patients: Clinical and Postmortem Characterization: Michael Davidson and Vahram Haroutunian

Psychotropic Drug Metabolism in Old Age: Principles and Problems of Assessment: Lisa L. von Moltke, David J. Greenblatt, Jerold S. Harmatz and Richard I. Shader

revised Pharmacological Treatment of Depression in Late Life: Carl Salzman, Lon S. Schneider, and George S. Alexopoulos

Neurologic Disorders

Parkinson's Disease: Amos D. Korczyn

Tardive Dyskinesia: Epidemiological and Clinical Presentation: John M. Kane. M.D.

Tardive Dyskinesia: Pathophysiology: Daniel E. Casey

The Treatment of Tardive Dyskinesias: George Gardos and Jonathan O. Cole

Multi-Infarct Dementia: David S. Geldmacher and Peter J. Whitehouse

Prion Diseases: Stephen J. DeArmond and Stanley B. Prusiner

revised Amyotrophic Lateral Sclerosis, Glutamate, and Oxidative Stress: Andreas Plaitakis and P. Shashidharan

Neuropsychiatric Manifestations of HIV-1 Infection and AIDS: Robert A. Stern, Diana O. Perkins, and Dwight L. Evans

Potential Mechanisms of Neurologic Disease in HIV Infection: Melvyn P. Heyes

new Huntington's Disease: Jang-Ho J. Cha and Anne B. Young

Personality Disorders

The Neuropsychopharmacology of Personality Disorders: Emil F. Coccaro and Larry J. Siever

Eating Disorders

Psychopharmacology of Anorexia Nervosa, Bulimia Nervosa, and Binge Eating : B. Timothy Walsh and Michael J. Devli

new Obesity, Fat Intake and Chronic Disease: George A. Bray

Basic Biological Overview of Eating Disorders: Katherine A. Halmi

Pharmacological Treatment of Obesity: Gerald Curzonand E. Leigh Gibson

Sleep Disorders

Disordered Sleep: Developmental and Biopsychosocial Perspectives on the Diagnosis and Treatment of Persistent Insomnia: Charles F. Reynolds III, Daniel J. Buysse, and David J. Kupfer

Childhood Disorders

Early-Onset Mood Disorder: David A. Brent, M.D., Neal Ryan,M.D., Ronald Dahl, M.D., and Boris Birmaher, M.D.

The Interface of Genetics, Neuroimaging and Neurochemistry in Attention-Deficit Hyperactivity Disorder: Monique Ernst and Alan Zametkin

revised Autism and Pervasive Developmental Disorders: Linda J. Lotspeich

revised Tic Disorders: James F. Leckman, Bradley S. Peterson, and David L. Pauls

revised Eating Disturbances and Eating Disorders in Childhood: Regina C. Casper

Childhood Anxiety Disorders: Susan Jo Perlmutter, M.D.

Substance Abuse

Cocaine: Chris-Ellyn Johanson and Charles R. Schuster

Caffeine A Drug of Abuse?: Roland R. Griffiths and Geoffrey K. Mumford

Chronic Amphetamine Use and Abuse: Everett H. Ellinwood, M.D., George. King, Ph.D., Tong H. Lee, M.D., Ph.D.

Pathophysiology of Tobacco Dependence: Jack E. Henningfield, Leslie M. Schuh, and Murray E. Jarvik

Opioids: George E. Bigelow and Kenzie L. Preston

Pharmacotherapy of Alcoholism: Charles P. O'Brien, Margaret R. Rukstalis, and Michael F. Stromberg

Marijuana: Billy R. Martin

Phencyclidine: David A. Gorelick and Robert L. Balster

Abuse and Therapeutic Use of Benzodiazepines and Benzodiazepine-Like Drugs: James H. Woods, Jonathan L. Katz, Gail Winger

Barbiturates: Neil Harrison, Wallace Mendelson and Harriet de Wit

Genetic Influences in Drug Abuse: George R. Uhl, Gregory I. Elmer, Michele C. LaBuda, and Roy W. Pickens

Behavioral Treatment of Drug and Alcohol Abuse: Maxine L. Stitzer and Stephen T. Higgins

Integrative Concepts

Genetics: Raymond R. Crowe, MD

Strategies for Multimodality Research: Ellen Frank, David J. Kupfer, and Jordan Karp

Methodological and Statistical Progress in Psychiatric Clinical Research: A Statistician's Perspective: Helena Chmura Kraemer, Ph.D.


New Drug Design in Psychopharmacology: The Impact of Molecular Biology: John F. Tallman and Svein G. Dahl

Ethical Issues in Genetic Screening and Testing, Gene Therapy, and Scientific Conduct: Lisa S. Parker and Elizabeth Gettig

Psychiatric Genetic Counseling: Debby Tsuang, M.D., M.Sc., Stephen V. Faraone, Ph.D., and Ming T. Tsuang, MD, Ph.D. D.Sc., FRCPsych.

new The Economics of Psychotropic Drug Development: Joseph A. DiMasi and Louis Lasagna

Economic Evaluation of Drug Treatment for Psychiatric Disorders: The New Clinical Trial Protocol: Gary A. Zarkin, Ph.D.

Ethnicity, Culture, and Psychopharmacology: Keh-Ming Lin and Russell E. Poland

Neurobiology of Suicide & Aggression: J. John Mann, M.D.


Conflict of Interest

Guidelines applicable to all Publications Editors, including Deputy and Associate Editors, are detailed in the Conflict of Interest Policy for ACNP Council, Committees and all Editors.

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