Neuroregulation of Autonomic, Endocrine and …978-1-4613-2315-0/1.pdf · Neuroregulation of...

Neuroregulation of Autonomic, Endocrine and Immune Systems


edited by

Robert C.A. Frederickson Monsanto Company St. Louis, Missouri

Co-editors

Hugh C. Hendrie Joseph N. Hingtgen Morris H. Aprison

Indiana University School of Medicine Indianapolis, Indiana

Martinus Nijhoff Publishing a member of the Kluwer Academic Publishers Group

Boston / Dordrecht / Lancaster

Distributors for North America: Kluwer Academic Publishers 190 Derby Street Hingham, Massachusetts 02043, USA

Distributors for the UK and Ireland: Kluwer Academic Publishers MTP Press Limited Falcon House, Queen Square Lancaster LAIIRN, UNITED KINGDOM

Distributors for all other countries: Kluwer Academic Publishers Group Distribution Centre Post Office Box 322 3300 AH Dordrecht, THE NETHERLANDS

Library of Congress Cataloging-in-Publication Data

Neuroregulation of autonomic, endocrine, and immune systems

Includes index. I. Medicine, Psychosomatic-Congresses. 2. Psycho

neuroendocrinology-Congresses. 3. Neuroimmunology -Congresses. 4. Neuroendocrinology-Congresses. 5. Stress (Physiology)-Congresses. 6. Neurotransmitters -Congresses. I. Frederickson, Robert C.A. RC49.N49 1986 612 '.8 86-1431 ISBN-13:978-1-4612-9424-5 e-ISBN-13:978-1-4613-2315-0 DOl: 10.1007/978-1-4613-2315-0

Copyright © 1986 by Martinus Nijhoff Publishing, Boston Softcover reprint of the hardcover 1st edition 1986

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, photocopying, recording, or otherwise, without written permission of the Publisher, Martinus Nijhoff Publishing, 190 Derby Street, Hingham, Massachusetts 02043.

CONTENTS

Local Organizing Committee x External Advisory Committee x List of Participants xi Preface xvii Acknowledgments xix

Introduction - The Brain and the Biopsychosocial Approach to Medicine H. C. Hendrie

I CENTRAL NEUROTRANSMITTER SYSTEMS: DISTRIBUTION AND FUNCTION

2 Brain Monoaminergic Neurons: Distribution and Function in Relation to Regulation of Autonomic, Neuroendocrine and Immune Systems 9 R. W. Fuller

3 Distribution and Function of Amino Acid Neurotransmitters: Roles in Central Modulation of the Autonomic, Neuroendocrine and Immune Systems 29 l.A. DiMicco and M.H. Aprison

4 Neuropeptides and Their Possible Role as Auxiliary Messengers 61 T. H6k/elt, T. Melander, W. Staines, S. Weisen/eld-Hallin, A.-L. Hulting, S. Werner, P. Eneroth, l. -A. Lindgren, B. Samuelsson, C. Patrono, A. Rokaeus, l. Fahrenkrug, S.A. loseph, and l.A. Fischer

5 Plasticity of Neuronal Interactions: Monoamines and Neuropeptides 89 l.R. Sladek, P.F. Avrich, l. Collier, B.J. Davis, and C.l. Phelps

II THE A UTONOMIC SYSTEM 6 An Overview of the Efferent Autonomic Nervous System 109 S. Y. Felten, S.L. Carlson, D.L. Bellinger, and D.L. Felten

7 Brain Stem Mechanisms Regulating the Tonic and Reflex Control of Blood Pressure 127 D. Reis

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8 Opiods and Other Neuropeptides: Functional Interactions with Autonomic Systems 151 J. W. Holaday

9 Assessment of Autonomic Function in Essential Hypertension 183 S. Julius, B. Egan, and A. Hinderliter

10 The Importance of Autonomic Innervation of the Heart in the Genesis of Cardiac Arrhythmias 199 D.P. Zipes, M.J. Barber, N. Takahashi, and R.F. Gilmour, Jr.

III THE NEUROENDOCRINE SYSTEM 11 The Neuroendocrine System 223 W.F. Ganong

12 Monoaminergic Control of the Neuroendocrine System 243 J.A. Clemens

13 Thyrotropin-Releasing Hormone: Localization of Specific Hypothalamic and Extrahypothalamic Sites of CNS Modulation 265 M.J. Kubek

14 Neurohumoral Mechanisms in Asthma 303 S. C. Lazarus

IV THE IMMUNE SYSTEM 15 An Overview of the Immune Response or An Immunologist's View of the Nervous System Control of the Immune System 323 E.S. Golub

16 Interactions Among the Nervous, Endocrine and Immune Systems (NIM) 329 N.H. Spector

17 Stress, Opioid Peptides and Immune Function 343 Y. Shavit, J. W. Lewis, G. W. Terman, R.P. Gale, and J.C. Liebeskind

18 Stress, Depression and Immunity 367 M. Stein, S.J. Schleifer, and S.E. Keller

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V THE CENTRAL NERVOUS SYSTEM AND DISEASE 19 Overview of Central Control Mechanisms and Disease Development 391 H. Weiner

20 Biosynthesis and Targeting of {1-Endorphin 405 D.G. Smyth

21 Endorphins-Development of the Therapeutic Utility of Enkephalin Analogues 421 R.C.A. Frederickson

22 A Hypersensitive Serotonergic Receptor Theory of Depression: The Role of Stress 443 M.H. Aprison and 1.N. Hingtgen

23 Neuropeptides and other Mediators in the Central Nervous System 461 F.E. Bloom

VI SHORT COMMUNICA TJONS 24 Glutamate, GABA and Cholinergic Systems in the NTS, DMN and Hypoglossal Nucleus of the Rat 475 1.R. Simon, S.K. DiMicco, and M.H. Aprison

25 Single Unit Responses to Catecholamines in the Nucleus Tractus Solitarii and Dorsal Motor Nucleus of the Vagus 483 P.D. Feldman and H.c. Moises

26 In Vivo Cardiovascular Responses to Isoproterenol, Dopamine and Tyramine Following Prolonged Infusion of Isoproterenol 487 1.S. Hayes, G.D. Pollock, and R. W. Fuller

27 Cardiac Arrhythmia in Sleep Apnea Syndromes: State, Sinus Arrhythmia, and Concurrent Pathophysiology 493 R.B. Trelease, E.G. Zimmerman, D.L. Arand, R.M. Harper, R.E. Hall, and G. Heit

28 Does Mental Stress Lead to Permanent Vascular Alterations? 499 S.M. Mueller, D.M. Latimer, and B.J. Watts

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29 Immobilisation Stress in Rats: Gastric Mucosal Depletion and Effects of Central Noradrenaline Depletion 503 R. Murison, H.K. Bakke, B. Walther, and H. Ursin

30 Glucagon and Glucagon-Like Peptide Receptor Localization and Characterization in Rat Brain and Pituitary 509 R.S. Gurd and N.M. Hoosein

31 Appetitive Behavior May Serve as a Model for Studying the Neural Facilitation and Inhibition of Plasma Corticosterone Levels in Rats 515 G. Coover, C. Lints, D. Stearn, and G. T. Satterfield

32 Suspense Increases Salivary Cortisol 521 D.H. Hellhammer, K. Rottger, l. Lorenzen, and W. Hubert

33 Corticosterone Responses in Maternal and Neonatal Plasma Induced by Tryptophan Diets Fed During the Third Trimester 525 M. Sakuma

34 Influence of a-Endorphin on the Antigen-Induced PFC Response of Human Blood B Lymphocytes in vitro 533 C.J. Heijnen, N. de Fouw, and R.E. Ballieux

35 Interaction Between the Central Nervous System and the Immune System: The Influence of a Short and Mild Emotional Stress on the Proliferative Response of Rat Spleen Cells 539 C.J. Heijnen, G. Croiset, C. Bevers, H.D. Veldhuis, D. de Weid, and R.E. Ballieux

36 In Vivo Voltammetric Evidence that d-Amphetamine and Phenethylamine Release Ascorbic Acid Into Striatal Extracellular Fluid 551 l.A. Clemens and L.A. Phebus

37 Serotonin, Imipramine Binding, Cortisol and Anxiety in Humans Under Stress 559 D.D. Davis, P.A. Shea, S.R. Dunlop, H. Brittain, and H.C. Hendrie

38 Bioavailability of the Opioid Peptide, Metkephamid 565 D.R. Holland, R.C.A. Frederickson, K.S.E. Su, and C.J. ParU

39 The Opioid Antagonist, ~-Funaltrexamine (~-FNA) Differentially Antagonizes the Analgesic Activity of Morphine and Metkephamid (L YI27623), A Methionine-Enkephalin Analog 573 M.D. Hynes, D.M. Zimmerman, P.D. Gesel/chen, and R.C.A. Frederickson

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40 Temperature and Feeding Responses of Normal and Dystrophic Hamsters to Morphine 587 l.A. Thornhill and M. Desautels

Index 593

LOCAL ORGANIZING COMMITTEE

H. C. Hendrie, M. B. Ch.B. Chairman and Albert B. Sterne Professor of Psgchiatry

Indiana Universitg School of Medicine

M. H. Aprison, Ph.D. Distinguished Professor of Neurobiology and Biochemistry


R. C. A. Frederickson, Ph.D. Senior Director, Central Nervous Sgstem Research

Searle Research & Development G. D. Searle & Co.

J. N. Hingtgen, ph.D. Professor of Psgchology and Neurobiology


EXTERNAL ADVISORY COMMITTEE

D. L. Felton, M.D., Ph.D. Universitg of Rochester School of Medicine

Rochester, New York

D. H. Hellhammer, Ph.D. Universitg of Munster and Max Plank Institute

MUnster, Federal Republic of Germang

R. C. Murison, Ph.D. universitg of Bergen

Bergen, Norwag

H. Weiner, M.D. UCLA School of Medicine Los Angeles, California

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LIST OF PARTICIPANTS

M. B. Aprison Departments of Pharmacology & Toxicology & Psgchiatry Program in Medical Neurobiologg Indiana Vniversitg School of Medicine Indianapolis, Indiana 46223

D. L. Arand UCLA Sleep Disorders Clinic Reed Neurological Research Center Los Angeles, California 90024

Paul F. Arvich Department of Neurobiology and

Anatomy Vniversitg of Rochester School of

Medicine and Dentistry Rochester, New York 14642

B. K. Bakke Institute of Phgsiological

Psgchologg and Biochemistry Vniversitg of Bergen Arstadveien 21, 5000 Bergen, Norwag

R. E. Ballieux Department of Clinical Immunology Vniversitg Hospital utrecht, The Netherlands

Michael J. Barber The Krannert Institute of Cardiology Departments of Medicine,

Pharmacology and Toxicologg Indiana Vniversitg School of Medicine and Richard C. Roudebush veterans

Administration Medical Center Indianapolis, Indiana

Denise Lorton Bellinger Department of Anatomy Vniversitg of Rochester School

of Medicine Rochester, New York 14642

caroline Bevers Department of Immunologg Vniversitg Hospital for Children

and Youth Vniversitg of Utrecht Utrecht, The Netherlands

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Floyd E. Bloom Division of Preclinical Neuroscience

and Endocrinologg scripps Clinic and Research

Foundation 10666 North Torreg Pines Road La Jolla, California 92037

B. Brittain Department of Psgchiatry Indiana Vniversitg School of Medicine Indianapolis, Indiana 46223

Sonia L. Carlson Department of Anatomy Vniversitg of Rochester School of

Medicine Rochester, New York 14642

James A. Clemens The Lillg Research Laboratories Eli Lillg and Compang Indianapolis, Indiana 46285

Timothy J. Collier Department of Neurobiologg and

Anatomy Vniversitg of Rochester School of


Gary Coover Department of Psgchologg Northern Illinois Vniversitg Dekalb, Illinois 60015

Gerda Croiset Departments of Immunologg and

Clinical Immunologg Universitg Hospital for Children

and Youth and Universitg Hospital Universitg of Utrecht Utrecht, The Netherlands

Barbara J. Davis Department of Neurobiologg and

Anatomy Universitg of Rochester School of


D. Davis Department of Psychiatry Indiana University School of Medicine Indianapolis, Indiana 26223

Nanneke de Fouw Department of Immunology University Hospital for Children

and Youth ''Bet Wilhelmina Kinderziekenhuis"; Utracht, The Netherlands

M. Desautels Department of Physiology University of Saskatchewan Saskatoon, Saskatchewan,

Canada S7N OJl1O

D. De Wied Rudolf Magnus Institute for

Pharmacology University of utrecht Utrecht, The Netherlands

J. A. DiMicco Departments of Pharmacology & Toxicology & Psychiatry Program in Medical Neurobiology Indiana University School of Medicine Indianapolis, Indiana 46223

s. Dunlop Department of Psychiatry Indiana university School of Medicine Indianapolis, Indiana 46223

Brent Egan Division of Hypertension Department of Internal Medicine university of Michigan Medical Center Ann Arbor, Michigan

P. Eneroth Department of Endorinology and the

Hormone Laboratory Karolinska Hospital Stockholm, Sweden

J. Fahrendrug Department of Pharmacology Karolinska Institute Stockholm, Sweden Department of Clinical Chemistry Bispebjerg Hospital Copenhagen, Denmark

Peter D. Feldman Department of Physiology University of Michigan School of

Medicine Ann Arbor, Michigan 48109

David t. Felten Department of Anatomy Univers~ty of Rochester School of


Suzanne Y. Felten Department of Anatomy University of Rochester School of


J. A. Fischer Neuroendocrine Unit University of Rochester Rochester, New York

R. C. A. Frederickson Central Nervous System Research Searle Research and Development G. D. Searle & Co. Skokie, Illinois 60077

Ray W. Fuller Lilly Research Laboratories Eli Lilly and Company Indianapolis, IN 46285

Robert Peter Gale Department of Medicine University of California Los Angeles, California 90024

William F. Ganong Department of Physiology University of California, San

Francisco San Francisco, California 94143

Paul D. Gessellchen Department of Central Nervous System

Research The Lilly Research Laboratories ELi J;.illy and Company Inianapolis, Indiana 47285

Robert F. Gilmour, Jr. The Krannert Institute of Cardiologg Departments of Medicine, Pharmacologg

and Toxicologg Indiana University School of Medicine

and Richard C. Roudebush Veterans Administration Medical Center

Indianapolis, Indiana

Edward S. Golub Department of Biological Sciences Purdue University West Lafayette, Indiana 49707

Ruth S. Gurd Medical Sciences Program and

Department of Chemistry Indiana University Bloomington, Indiana 47405

R. E. Hall UCLA Sleep Disorders Clinic Reed Neurological Research Center Los Angeles, California 90024

R. M. Harper UCLA Sleep Disorders Clinic Reed Neurological Research Center Los Angeles, California 90024

J. Scott Hayes Eli Lilly and Company Lilly Research Laboratories Departments of Cardiovascular

Pharmacologg and Central Nervous System Research

Indianapolis, Indiana 46285

Alan Hinderliter Division of Hypertension Department of Internal Medicine University of Michigan Medical Center Ann Arbor, Michigan

Cobi J. Heijnen Department of Immunologg University Hospital for Children

and Youth "Het Wilhelmina Kinderziekenhuis"i Utrecht, The Netherlands

G. Heit UCLA Sleep Disorders Clinic Reed Neurological Research Center Los Angeles, California 90024

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D. H. Hellhammer Institute for Psychologg University of Munster, F. R. Germany

Hugh C. Hendrie, M.B. Ch.B. Department of Psychiatry Indiana University School of Medicine Indianapolis, Indiana 46223

Joseph N. Hingtgen Section of Applied and Theoretical

Neurobiologg The Institute of Psychiatric Research

and Departments of Psychiatry and Biochemistry

Indiana University School of Medicine Indiana University Medical Center Indianapolis, Indiana 46223

T. Hokfelt Department of Histologg Karolinska Institute Stockholm, Sweden

John W. Holaday Neuropharmacologg Branch Department of Medical Neurosciences Division of Neuropsychiatry Walter Reed Army Institute of

Research Washington, DC 20307-5100

D. R. Holland Lilly Research Laboratories Eli Lilly and Company Indianapolis, Indiana 46285

Naseema M. Hoosein Medical Sciences Program and Department of Chemistry Indiana University Bloomington, Indiana 47405

W. Hubert Institute for Psychologg University of Munster, F.R. Germany

A.-L. Hulting Department of Endocrinologg and the

Hormone Laboratory Karolinska Hospital Stockholm, Sweden

Martin D. Hynes Department of Central Nervous System

Research The Lilly Research Laboratories Eli Lilly and Company Indianapolis, Indiana 46285

S. A. Joseph Neuroendocrine Unit University of Rochester Rochester, New York

stevo Julius Division of Hypertension Department of Internal Medicine University of Michigan Medical Center Ann Arbor, Michigan

steven E. Keller Department of Psychiatry Mount Sinai School of Medicine City University of New York New York, New York 10029

Michael J. Kubek Departments of Anatomy and Psychiatry Indiana University School of Medicine & R.L. Roudebush V.A. Medical Center Indianapolis, Indiana 46223

Deborah M. Latimer Departments of Neurology and

Physiology Indiana University school of Medicine Regenstrief Health Center 1001 11'. lOth st. Indianapolis, Indiana 46202

stephen C. Lazarus cardiovascular Research Institute University of California, San

Francisco San Francisco, California 94143

James W. Lewis Department of Psychology University of California Los Angeles, California 90024

John C. Liebeskind Department of Psychology University of California Los Angeles, California 90024

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J.-A. Lindgren Department of Physiological Chemistry Karolinska Institute Stockholm, Sweden

Carlton Lints Department of Psychology Northern Illinois University Dekalb, Illinois 60015

J. Lorenzen Institute for Psychology University of Munster, F.R. Germany

T. Melander Department of Histology Karolinska Institute Stockholm, Sweden

Hylan Moises Department of Physiology University of Michigan

School of Medicine Ann Arbor, Michigan 48109

Shirley M. Mueller, M.D. Department of Neurology

and Physiology Indiana University School of Medicine

Regenstrief Health Center 1001 11'. 10th Street Indianapolis, Indiana 46202

R. Murison Institute of Physiological Psychology and Biochemistry

University of Bergen Arstadveien 21, 5000 Bergen, Norway

C. J. Parli Lilly Research Laboratories Eli Lilly and Company Indianapolis, Indiana 46285

C. Patrono Department of Pharmacology Catholic University Rome, Italy

L. A. Phebus The Lilly Research Laboratories Eli Lilly and Company Indianapolis, Indiana 46285

Carol J. Phelps Department of Neurobiology and

Anatomg university of Rochester School of


G. Donald Pollock Department of Cardiovascular Research Eli Lilly and Company Indianapolis, Indiana 46285

Donald J. Reis Laboratory of Neurobiology Cornell university Medical College New York, NY 10021

A. Rokaeus Department of Pharmacology Karolinska Institute Stockholm, Sweden

K. Rottger Institute for Journalism university of Munster F.R. Germany

M. Sakuma, M.D., Ph.D. Department of Psychiatry Wayne State university Detroit, Michigan 48207

B. Samuels son Department of Physiological Chemistry Karolinska Institute Stockholm, Sweden

G. Thomas Satterfield Department of Psychology Northern Illinois university Dekalb, Illinois 60115

Steven J. Schleifer, M.D. Department of Psychiatry Mt. Sinai School of Medicine city university of New York New York, New York 10029

Yehuda Shavit Department of Psychology university of California Los Angeles, California 90024

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P. Shea Department of Psychiatry Indiana university School of Medicine

Indianapolis, Indiana 46223

J. R. Simon Institute of Psychiatric Research Indiana university School of Medicine Indianapolis, Indiana 46223

John R. Sladek, Jr. Department of Neurobiology and Anatomg university of Rochester School of


D. G. Smyth National Institute for Medical

Research The Ridgeway London, England NW7 1AA

Novera Herbert Spector Fundamental Neurosciences Program NINCDS, National Institutes of Health Bethesda, Maryland 22205

W. Staines Department of Psychiatry Division of Neurological Sciences university of British Columbia Vancouver, Canada

Deborah Stearn Department of Psychology Northern Illinois university Dekalb, Illinois 60115

Marvin Stein, M.D. Department of Psychiatry Mt. Sinai School of Medicine City university of New York New York, New York 10029

K. S. E. Su Lilly Research Laboratories Eli Lilly and Company Indianapolis, Indiana 46285

Nobuhiro Takahashi The Krannert Institute of Cardiology Departments of Medicine, Pharmacology

and Toxicology Indiana University School of Medicine



Gregory W. Terman Department of Psychology University of California Los Angeles, California 90024

J. A. Thornhill Department of Physiology University of Saskatchewan Saskatoon, Saskatchewan,

Canada S7N OliO

R. B. Trelease UCLA Sleep Disorders Clinic Reed Neurological Research Center

Los Angeles, California 90024

H. Ursin Institute of Physiological Psychology and Biochemistry


H. D. Veldhuis Rudolf Magnus Institute for Pharmacology

University of Utrecht Utrecht, The Netherlands

B. Walther Institute of Physiological Psychology and Biochemistry


Belinda J. Watts, M.S. Department of Neurology and Physiology

Indiana University School of Medicine

Regenstrief Health Center 1001 Ii. 10th Street Indianapolis, Indiana 46202

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Herbert Weiner, M.D. Department of Psychiatry, Brain Research Institute University of California school of Medicine


S. Werner Departments of Histology and

Endocrinology Karolinska Institute stockholm, Sweden

S. Wiesenfeld-Hallin Department of Clinical Neurophysiology Huddinge Hospital Stockholm, Sweden

Dennis M. Zimmerman Department of Central Nervous System Research

The Lilly Research Laboratories Eli Lilly and Company Indianapolis, Indiana 46285

E.G. Zimmerman, M.D.,Ph.D. UCLA Sleep Disorders Clinic Reed Neurological Research Center


Douglas P. Zipes The Krannert Institute of Cardiology Departments of Medicine, Pharmacology

and Toxicology Indiana University School of Medicine



PREFACE

Our understanding of the functioning of the brain has grown rapidly over the last decade or two. So has our recognition of the possible role of brain dysfunction in diseases considered earlier to be of peripheral or somatic origin. This culminates naturally in a focus on the nature of the influence of the brain on other systems such as the autonomic, neuroendocrine and immune systems. And we must come full circle and question the nature of the influence of these systems on the function of the brain. Thus, we gain a picture of a complex regulatory interaction, fine tuned in normal circumstances to provide each system with necessary information about the status of the other systems and the basis to respond appropriately to changes in each other.

This volume provides the proceedings of the first of a series of international symposia intended to review the state-of-the-art understanding and frontier exploration of the above described interregulatory phenomena, with some emphasis on the relevance of this information to the etiology and treatment of disease. The purpose of this first symposium was to lay the groundwork for this continuing endeavor. To accomplish such a goal required bringing together diverse multidisciplinary professionals - eg neurobiologists, immunologists, psychiatrists, cardiologists and students amongst others.

In order to facilitate understanding and communication wi thin such a diverse group the presentations were organized to provide coverage of each discipline from an overview of the background and present status of an area to the exploration of the newest developments. The presentation of the basic science in a given area, furthermore, was immediately followed by presentation of pertinent clinical papers to facilitate the

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evaluation of the progression of findings from the laboratory to medical practice.

It is intended that this approach will make the volume complete and self-contained and thus informative to the novice as well as the expert in any given field. It is our wish that this series thereby become an important definitive resource for understanding the interaction between the central nervous, autonomic, neuroendocrine and immune systems and how our scientific exploration of them is being organized to impact on our knowledge of the etiology of disease and its rational treatment.

Robert C. A. Frederickson, summer 1985 Hugh C. Hendrie Joseph N. Hingtgen Morris H. Aprison

ACKNOWLEDGEMENTS

These are the proceedings of the first of a continuing annual series of international symposia. The organizers are indebted to Eli Lilly and Company, Indianapolis, Indiana, the Norways Foundation and the Edward A. Block Fund, Department of Psychiatry, Indiana University school of Medicine and Monsanto Company for their generous support which made this endeavor possible. The organizers are further indebted to the participants whose talented efforts insured the success of this meeting.

The publication of this book has been facilitated by the provlslon of secretarial personnel and wordprocessing facili ties by Monsanto company. The editors are indebted to Mrs. Pat Kutey and Ms. Debbie Lix for their tireless efforts in preparing the final manuscripts, and to the publishers for their dedication to completing this project in a timely fashion.

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