Drugs and the Developing Brain PDF
Preview Drugs and the Developing Brain
Drugs and the Developing Brain ADVANCES IN BEHAVIORAL BIOLOGY Editorial Board: Jan Bures Institute of Physiology, Prague, Czechoslovakia Irwin Kopin Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland Bruce McEwen Department of Biology, Rockefeller University, New York, New York James McGaugh Department of Psychobiology, University of California, Irvine, California Karl Pribram Department of Psychology, Jordan Hall, Stanford University School of Medicine, Stanford, California Jay Rosenblatt Institute of Animal Behavior, Rutgers University, Newark, New Jersey Lawrence Weiskrantz Institute of Experimental Psychology, University of Oxford, Oxford, England Volume 1 • BRAIN CHEMISTRY AND MENTAL DISEASE Edited by Beng T. Ho and William M. Mcisaac· 1971 Volume 2 • NEUROBIOLOGY OF THE AMYGDALA Edited by Basil E. Eleftheriou • 1972 Volume 3 • AGING AND THE BRAIN Edited by Charles M. Gaitz • 1972 Volume 4 • THE CHEMISTRY OF MOOD, MOTIVATION, AND MEMORY Edited by James L. McGaugh • 1972 Volume 5 • INTERDISCIPLINARY INVESTIGATION OF THE BRAIN Edited by J. P. Nicholson' 1972 Volume 6 • PSYCHOPHARMACOLOGY AND AGING Edited by Carl Eisdorfer and William E. Fann • 1973 Volume 7 • CONTROL OF POSTURE AND LOCOMOTION Edited by R. B. Stein, K. G. Pearson, R. S. Smith, and J. B. Redford' 1973 Volume 8 • DRUGS AND THE DEVELOPING BRAIN Edited by Antonia Vernadakis and Norman Weiner· 1974 Volume 9 • PERSPECTIVES IN PRIMATE BIOLOGY Edited by A. B. Chiarelli· 1974 Drugs and the Developing Brain Edited by Antonia Vernadakis Associate Professor Departments of Psychiatry and Pharmacology and Norman Weiner Professor and Chairman Department of Pharmacology University of Colorado School of Medicine Denver, Colorado PLENUM PRESS • NEW YORK - LONDON Library of Congress Cataloging in Publication Data Main entry under title: Drugs and the developing brain. (Advances in behavioral biology, v. 8) Sponsored by Pfizer Pharmaceuticals. Includes bibliographies. 1. Neuro-psychopharmacology. 2. Developmental neurology. I. Vernadakis, Antonia, 1930- ed. II. Weiner, Norman, 1928- ed. III. Pfizer Pharmaceuticals. [DNLM: 1. Brain-Drug effects-Congresses. 2. Brain-Embryology-Congresses. 3. Brain Chemistry-Drug effects-Congresses. W3 AD215 v. 8 1972/WL300 S89d 1972] RM315.D83 615'.78 74-640 ISBN-13: 978-1-4684-3065-3 e-ISBN-13: 978-1-4684-3063-9 DOl: 10.1007/978-1-4684-3063-9 Proceedings of the symposium on "Drugs and the Developing Brain," held at the University of Colorado, School of Medicine, Denver, Colorado, December 18-20, 1972 © 1974 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1974 A Division of Plenum Publishing Corporation 227 West 17th Street, New York, N.Y. 10011 United Kingdom edition published by Plenum Press, London A Division of Plenum Publishing Company, Ltd. Davis House (4th Floor), 8 Scrubs Lane, Harlesden, London, NW10 6SE, England All rights reserved No part of this publication may be reproduced in any form without written permission from the publisher ACKNOWLEDGMENTS This symposium was sponsored by PFIZER PHARMACEUTICALS 235 East 42nd Street, New York, N.Y. The editors are grateful to Miss Marilyn Robbins for her assistance throughout the organization of the symposium and the preparation of the proceedings. v PREFACE The thalidomide tragedy which occurred slightly more than a decade ago made public officials and the general public acutely aware of the teratogenic potential of drugs. Although specialists in pharmacology and developmental biology had been studying this problem many years before, this catastrophic episode triggered the passage of legislation which required that information about the teratogenicity of drugs be produced before the drugs could be available to the general public. Gross deformities in man produced by drugs are frequently difficult to reproduce in experimental animals and the changes which are produced in other animals are frequently not translatable to humans. The problem of evaluating the potential that drugs have to produce gross malformations is small, however, compared to the evaluation of subtle but permanent behavioral effects which drugs may exert upon the developing organism. Nevertheless, many experimental studies in recent years indicate that subtle biochemical changes produced by drugs on brain tissue during critical periods of fetal or early post natal maturation may become manifest subsequently as behavioral deviations in early childhood or adolescence. Hyperkinetic disorders, epilepsies and other developmental disabilities may have a subtle biochemical imbalance, perhaps drug induced, as an underlying factor. This symposium was organized with the intent of bringing to gether prominent investigators who are working in different aspects of brain development and who are interested in the effects of drugs on the developing brain in order to discuss their findings, pro pose new theories, and open new avenues for future research. It is only by discussing and exploring the enormous complexities of brain development, the critical periods during which the develop ing brain is most vulnerable to exogenous agents, and the molecular basis for brain vulnerability, that we will begin to understand the nature and the significance of the actions of drugs on the developing brain. vii viii PREFACE This symposium focuses on brain development, both at the cell ular and organismic levels and covers such physiological aspects as electrical activity, myelinogenesis, neurotransmission, the blood-brain-barrier, the metabolism of the brain and the influence of drugs, hormones and environment (e.g., high altitude) thereon. An attempt has been made to relate molecular neurobiology to developmental disabilities such as epilepsy and the hyperkinetic syndrome. Evaluation of the therapy of these disorders also is discussed. Although not all aspects of brain development have been covered in this symposium, we hope that these proceedings offer basic information and present experimental models which can be used to obtain information useful for clinical application. Finally, we hope that these proceedings will stimulate further research in the vitally important and growing field of Develop mental Neuropharmacology. Antonia Vernadakis and Norman Weiner CONTENTS CNS DRUGS: FUNCTIONAL DEVELOPMENT Dominick P. Purpura, Chairman DOMINICK P. PURPURA 3 Development of Synaptic Substrates for Drug Actions in Immature Brain. STANLEY M. CRAIN 29 Selective Depression of Organotypic Bioelectric Activities of CNS Tissue Cultures by Pharmacologic and Metabolic Agents. CNS DRUGS: BEHAVIORAL DEVELOPMENT C.O. Rutledge, Chairman C.O. RUTLEDGE 61 Factors Influencing the Effects of Drugs Administered During Development on Adult Behavior. 67 RICHARD E. WHALEN Gonadal Hormones and the Developing Brain. SHELDON B. SPARBER 81 Postnatal Behavioral Effects of In Utero Exposure to Drugs Which Modify Catecholamines and/or Serotonin. DEVELOPMENTAL ASPECTS OF NEUROTRANSMISSION Norman Weiner, Chairman NORMAN WEINER 105 Neurotransmitter Systems in the Central Nervous System. ANTONIA VERNADAKIS 133 Uptak e and S t orage 0 f 3 H-Norep.l neph rl'n e l. n th e Ce reb ra 1 Hemispheres and Cerebellum of Chicks During Embryonic Development and Early Posthatching. ix x CONTENTS J.C. WAYMIRE, A. VERNADAKIS and N. WEINER 149 Studies on the Development of Tyrosine Hydroxylase, Monoamine Oxidase and Aromatic-L-Amino Acid Decarboxylase in Several Regions of the Chick B~ain. VELAYUHAN NAIR 171 Prenatal Exposure to Drugs: Effect on the Development of Brain Monoamine Systems. BERNARD L. MIRKIN 199 Chromogranins and Neurotransmitter Retention During Development of the Adrenergic Neuron. DRUG ACTIONS: BIOCHEMICAL DEVELOPMENT: (Enzymes, Amino Acids, Proteins and Nucleic Acids) Abel Lajtha, Chairman ABEL LAJTHA and DAVID DUNLOP 215 Alterations of Protein Metabolism During Development of the Brain. WILLIAMINA A. HIMWICH and JIMMIE M. DAVIS 231 Free Amino Acids in the Developing Brain as Affected by Drugs. DOHERTY B. HUDSON, BEVERLY J. MERRILL and LAURIE A. SANDS 243 Effects of Prenatal and Postnatal Nicotine Administration on Biochemical Aspects of Brain Development. DRUG ACTIONS: BIOCHEMICAL DEVELOPMENT: (Electrolytes, Acid-Base) Dixon M. Woodbury, Chairman DIXON M. WOODBURY 259 Maturation of the Blood-Brain and Blood-CSF Barriers. CONRAD E. JOHANSON and DIXON M. WOODBURY 281 Changes in CSF Flow and Extracellular Space in the Developing Rat. THEONY VALCANA 289 Developmental Changes in Ionic Composition of the Brain in Hypo and Hyperthyroidism. C.D. WITHROW 305 Some Aspects of Acid-Base Metabolism in the Immature Central Nervous System. CONTENTS xi DEVELOPMENTAL ASPECTS OF LEARNING AND MEMORY Samuel Barondes, Chairman JOSEPH ALTMAN, ROBERT L. BRUNNER, FATMA G. BULUT and 321 KIRAN SUDARSHAN The Development of Behavior in Normal and Brain-Damaged Infant Rats, Studied with Homing (Nest-Seeking) as Motivation. DRUG ACTIONS: MYELINOGENESIS J. Folch-Pi, Chairman J. FOLCH-PI 351 Proteolipids. ELIZABETH R. EINSTEIN 375 Protein and Enzyme Changes with Brain Development. ALAN PETERS 395 The Morphology of the Developing Myelin Sheath. ENVIRONMENT, HORMONES: BRAIN DEVELOPMENT Paola S. Timiras, Chairman PAOLA S. TIMIRAS 417 Developmental Changes in the Responsivity of the Brain to Endogenous and Exogenous Factors. EVANGELOS A. PETROPOULOS and PAOLA S. TIMIRAS 429 Effects of Hypoxic Environment on Prenatal Brain Development: Recent Evidence Versus Earlier Dogma. DONALD H. FORD 451 Thyroid Hormones in Relation to Development of the Nervous System. THERAPEUTICS J. Gordon Millichap, Chairman 475 J. GORDON MILLICHAP Neuropharmacology of Hyperkinetic Behavior: Response to Methylphenidate Correlated with Degree of Activity and Brain Damage. JOHN W. OLNEY 489 Occult Mechanisms of Brain Development.
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