Current Developments in Psychopharmacology

Editorial AdYlsory Board

L. Cook (Nutley) J.M.R. Delgado (Madrid) M. Fink (Stony Brook) M. Jouvet (Lyon) L. Manara (Milan) J. Mendels (Philadelphia) M. Sandler (London) S. Snyder (Baltimore)

Executive Secretary

L. Morgese

Current Developments in Psychopharmacology Volume 6

EDITORS Walter B. EIsman Departments of Psychology & Biochemistry Queens College of the City University of New York, Flushing, N.Y.

L VaizeUi Section of Neuropsychopharmacology Mario Negri Institute for Pharmacological Research Milan, Italy

SP IIII11 SP MEDICAL & SCIENTIFIC BOOKS New York

Copyright © 1981 Spectrum Publications, Inc. Softcover reprint of the hardcover 1 st edition 1981

All rights reserved. No part of this book may be reproduced in any form, by photostat, microform, retrieval system, or any other means, without the prior written permission of the publisher.

Spectrum Publications, Inc. 175-20 Wexford Terrace, Jamaica, New York 11432

ISBN-13: 978-94-011-8125-9 e-ISBN-13: 978-94-011-8123-5 DOl: 10.1007/978-94-011-8123-5

Library of Congress Catalogue Card Number: 75-502

CURRENT DEVELOPMENTS IN PSYCHOPHARMACOLOGY

Volume 1 Dopamine Receptors and Their Role in Brain Function (Barnett); Brain Serotonergic and Catecholamine Systems: Facts and Hypothesis (Kostowski); Hippocampal and Autonomic Pharmacology in Performance and Learning (Izquierdo); Pharmacological and Neurochemical Approaches to Memory Trace Retrieval (flyutchenok); Cerebral Biochemical and Pharma­cological Changes in Differentially Housed Mice (DeFeudis); Rubidium in Psychiatry and Medi­cine: An Overview (Meltzer and Fieve); Clinical Psychopharmacology of the Affective Disorders (Abrams); Drug Effects in the Assessment of Affective States in Man (Gottschalk); Cerebral Electrometry in Phase-I Assessment of Psychoactive Drugs (Fink); Subject Index; Author Index

Volume 2 Studies of Central Cholinergic Neurons (Kuhar, Simon and Rommelspacher); F1urothyl­Pharmacology of Seizures in Animals and Man (Adler); The Clinical Use of F1urothyl (Small and Small); The Action of Central Nervous System Stimulant Drugs: A General Theory Con­cerning Amphetamine Effects (Lyon and Robbins); Advances in the Search for Improved Neuroleptic Drugs (Jan"sen and Van Bever); Sensory Psychopharmacology (Robinson and Sabat); Mania, Depression, and Brain Dopamine (Randrup, Munkvad, Fog, Gerlach, Molander, Kjellberg and Scheel-Kruger)

Volume 3 Amnesia and the Biology of Memory (Squire); Cycloheximide: Mechanisms of its Amnesic Effect (Nakajima); Piracetam: Nootropic Pharmacology of Neurointegrative Activity (Giurgea); Dopaminergic Drug Effects upon Serotoninergic Neurons (Maj); Neurotransmitter Regulation of Pituitary S.ecretion (Rose and Ganong); Aminergic Factors in Mental lllness (Berger); Mech­anisms of Lithium Toxicity Development in Rats (Thomsen, Olesen and Jensen); Drug Therapy in Depressive States: Factors in Suicide Prevention (Poeldinger); Drug Induced Aggression (Gianutsos and Lal)

Volume 4 Opiate Receptors in the Central Nervous System (Simon); Pharmacological and Biochemical Studies with ~~arboline Analogs (Ho); Recent Advances in Genetics and Psychopharmacology (Mendlewicz); Psychopharmacology of Aging: Current Trends (Sathananthan, Gershon, and Fe"is); Catecholamines and Behavior (Engel and Carlsson); Neuropharmacology of Hyper­kinesis (Si/bergeld); LOlJg Term Treatment with Neuroleptics in Psychiatry (Shepherd and Watt); Precipitated Morphine Withdrawal in Rats as a Tool in Opiate Research (Blasig and Herz); Tricyclic Antidepressants: A Review of Their Toxicology (Fiori)

Volume 5

The Pharmacology of Isolation-Induced Aggressive Behavior in Mice (Malick); Neurochemical Issues in Animal and Human Behavior (Valzelli); Circadian Rhythms in Manic-Melancholic Disorders (Mellerup and Rafaelsen); Pituitary Hormones and Amnesia (Rigter and Riezen); The Effects of D-Amphetamine on Dopaminergic Regulated Mechanism of Physiological and Behavioral Thermoregulation (Yehuda); Metabolism and Functions of Histamine in the Brain (Schwartz. Barhin, Baudr)" Gargarg. Martre,l', Pollard. and Verdiere); Psychobiological Interactions and Schizophrenia (Shore); Serotonin and Affective Disorders (Burns and Mendels); Clinical Language and Communication as a Tool of Psychopharmacological Research (Andreoli and Mafrei); Sex Steroid Control of Intermale Fighting in Mice (Brain and Bowden)

Preface

The areas of experimental and clinical psychopharmacology have continued to grow in terms of the numbers of studies appearing in the literature as well as the activity generated by other disciplines that has influenced the output of behavioral pharmacology research. Psychoactive drugs have been considered for their comparative effects upon selected behaviors or for their effect upon diverse behaviors. Behavioral circum­stances certainly influence not only the metabolism and action of psycho­tropic drugs behaviorally, but also the disposition of these agents and/ or their metabolites in regions of the central nervous system. There can hardly be a psychopharmacology without a neuropharmacology, and the latter would seem to depend upon a neurochemistry. There would appear to be variables that exert potent influences upon the disposition and action of psychotropic drugs, that also relate quite directly to their effects upon behavior; these include drug interactions, nutritional status, environmental effects such as temperature, photic and tactile stimulation, and stress, and the basal status upon which such drug treatment is superimposed.

In this volume of Current Developments in Psychopharmacology, which will be the last to appear in this format, we have sought to focus upon a series of current topical reviews that highlight representative areas of experimental and clinical research activity in psychopharmacology. In the first chapter, Dr. Lagerspetz reviews a frequently neglected aspect of psychopharmacological research-the actions of psychoactive agents upon the nervous system and behavior of non-mammalian species. Such compar­ative psychopharmacology presents a particularly fascinating array of new behavioral methodologies as well as unique response categories altered by psychoactive agents, as well as emphasizing the highly relevant relationship between mechanisms of temperature regulation and the disposition and action of psychotropic agents. The role of genetic variables in determining the psychoactive effects of opiates, as detailed by Drs. Oliverio and Castel­lano, represents an important series of relationships between the basal chemical substrates upon which opiates act and changes that occur as a function of genetic differences. The implications for genetic bases of differences in tolerance, analgesic effects and addictive potential to opiates touches upon a variety of other issues to which the present chapter fundamentally relates.

In his chapter concerned with the behavioral effects of anticonvulsant drugs, Dr. Trimble highlights the behavioral effects and behavioral toxicity of these agents. The relevance of these drugs for psychiatric disorders represents an area too often overlooked-both in terms of therapeutic benefit as well as symptom exacerbation. There has been little said of anticonvulsant-psychotropic drug interactions on a behavioral or neurologi­cal level. The present chapter serves to clarify this issue. One issue of cardinal import to the clinician employing neuroleptic agents is their capacity to induce disorders of involuntary movements; such drug-induced tardive dyskinesia is the subject of Dr. Hoh's chapter in this volume. The mechanisms underlying tardive dyskinesia and how this entity differs from other movement disorders is clearly explicated. Moreover, attention to the prevention and treatment of tardive dyskinesia takes into account the mechanisms related to this entity as well as some of the bases for psycho­tropic drug action and central mechanisms for movement and movement disorders.

The prominence of smoking and the effects of nicotine in the scientific, clinical, as well as popular literature emphasizes the significance of the behavior and the drug across a broad spectrum of issues in health and disease. Questions regarding the why's of smoking behavior and the effects of nicotine have long concerned the researcher and the clinician. In their chapter on this subject, Drs. Kumar and Lader consider various aspects of nicotine in maintaining smoking behavior and how the behavioral effects, via brain mechanisms, relate to the behavioral consequences of exposure to this drug and how its re-exposure relates to its effects.

The anti-manic effects of lithium salts are well known and these agents have become well accepted in the psychiatric pharmacopae. The use of lithium salts in the treatment of depression, however, has not been as uniformly accepted, either as a therapeutic approach of particular advan­tage, or as a treatment modality for depression that is readily consistent with theoretical grounds. In their chapter Drs. Arieli and Lepkifker have pro­vided a clinical-experimental framework within which the antidepressant actions of lithium are evaluated.

In the last chapter of this volume, Drs. Nagayama, Takagi, and Takahashi consider an important variable in the action of neuroleptic agents-the characteristics by which endogenous periodic variations provide for differences in their effects. Drug toxicity as well as behavioral efficacy appear to be regulated by the time period within which the drug is given and within which it is distributed, metabolized, and active. Both endogenous as well as exogenous regulatory mechanisms appear relevant to the onset, duration and efficacy of psychoactive drug effects, the basis for which may be sought on neurochemical, endocrinological, or neurophysiological bases, the interactions of which regulate the circadian influences upon drug action.

The seven chapters of this volume, although unique as far as chapters in prior volumes of this series are concerned, still constitute extensions of a continuum upon which the series was conceived, i.e., a comprehensive, yet contemporary, overview of the issues that comprise psychopharmacology. Although these issues have not fundamentally changed in the years since this series has been published, the variety of methodologies, the conceptual integration, and the psychopharmacopae have changed. This volume, while expanding the scope of subject coverage in the series, is also intended to serve the researcher and clinician as a perspective for issues of current focus and import for psychopharmacology.

The international scope of these volumes, represented by the roster of eminent contributors, has provided a rich resource of basic and clinical data. We thank the authors and we thank the members of the editorial advisory board who provided useful input and direction.

March, 1981 Walter B. Essman Flushing, N. Y.

Luigi Valzelli Milan, Italy

Contributors

ARIEL ARIELI Sanatorium Hahlama Venofesh N atanya, Israel

CLAUDIO CASTELLANO Istituto di Psicobiologia e Psicofarmacologia,

C.N.R. Rome, Italy

HlTOSHI ITOH Department of Neuropsychiatry School of Medicine, Keio University Tokyo, Japan

RAMESH KUMAR Department of Psychiatry Institute of Psychiatry University of London London, England

MALCOLM LADER Department of Psychiatry Institute of Psychiatry University of London London, England

KARl Y.H. LAGERSPETZ Zoophysiological Laboratory Department of Biology University of Turku Turku, Finland

ELIE LEPKIFKER Department of Psychiatry Chaim Sheba Medical Center Tel-Aviv University Medical School Tel-Hashomer, Israel

HARUO NAGA Y AMA Department of Neuropsychiatry Nagasaki University School of Medicine Nagasaki, Japan

ALBERTO OLIVERIO Istituto di Psicobiologia e Psicofarmacologia,

C.N.R. Rome, Italy

AKINORI TAKAGI Department of Neuropsychiatry Nagasaki University School of Medicine Nagasaki, Japan

RYO TAKAHASHI Department of Neuropsychiatry Nagasaki University School of Medicine Nagasaki. Japan

MICHAEL TRIMBLE The National Hospitals for Nervous Diseases London, England

Contents CHAPTER 1

Comparative Psychopharmacology Kari Y.H. Lagerspetz

A. Introduction, I B. Spontaneous Motor Activity, 6

1

C. Sedation in the Frog: A Screening Test for Tymoleptics, 10 D. Web-Building in Spiders, II E. Aggressive Behavior, 13 F. Learning and Memory, 18 G. Perspectives for Comparative Psychopharmacology, 30 H. Summary, 34 I. References, 35

CHAPTER 2 Behavioral Effects of Opiates: A Pharmacogenetic Analysis

Alberto Oliverio and Claudio Castellano

45

A. Individual and Species Differences in Drug Reactivity, 45 B. Species Differences in the Reactivity to Opiates, 46 C. The Use of Inbred Strains in Pharmacogenetic

Investigations, 49 D. A Pharmacogenetic Approach to Opiates, 51 E. Dopaminergic and Cholinergic Mechanisms in Relation to

Strain Differences in Opiates Effect, 57 F. Opiates Administration: Environmental Factors, 58 G. Summary, 59 H. References, 61

CHAPTER 3 Anticonvulsant Drugs, Behavior, and Cognitive Abilities

Michael Trimble

A. Introduction, 65

65

B. Drugs and Cognitive Behavior, 66 C. The Effects of Anticonvulsant Drugs on Behavior, 80 D. Mechanism of Interference with Cognitive Function and

Behavior, 84 E. References, 87

CHAPTER 4 Drug-Induced Tardive Dyskinesia

Hitoshi ltoh

A. Introduction, 94 B. Prevalence of Tardive Dyskinesia, 96 C. Clinical Features and Localization, 96 D. Patient Characteristics, 104 E. Causal Psychotropic Treatment, 108 F. Differential Diagnosis, III

93

G. Relationship Between Tardive Dyskinesia and Other Drug­Induced Extrapyramidal Symptoms, 112

H. Relationship Between Tardive Dyskinesia, Levodopa-Induced Dyskinesia, and Huntington's Chorea, II4

I. Reversibility of Tardive Dyskinesia, II7 1. Treatments and Prophylaxis of Tardive Dyskinesia, 120 K. Conclusion, 121 L. References, 122

CHAPTER 5 Nicotine and Smoking

R. Kumar and M. Lader

A. Introduction, 127 B. Studies in Animals, 128 C. Studies in Humans, 141 D. References, 158

CHAPTER 6 The Antidepressant Effect of Lithium

Ariel Arieli and Elie Lepkifker

A. Introduction, 165 B. The Overall Antidepressant Effect of Lithium, 166 C. Methods, 168

127

165

D. Results, 170 E. Further Clinical Problems, 181 F. References, 188

CHAPTER 7 Chronopharmacological Studies of 191 N euroleptics

Haruo Nagayama, Akinori Takagi, and Ryo Takahashi

A. Introduction, 191 B. Fluctuation of Psychotropic Drug Toxicity, According to

the Difference in TODA, 192 C. Fluctuation in Effect of Psychotropic Drugs Due to

Difference in TODA, 196 D. Circadian Fluctuation in Effects of Neuroleptics Induced

by Difference in TODA, 203 E. Comments, 210 F. References, 211

SUBJECT INDEX 215

AUTHOR INDEX 221