Neurobiology of the Trace Amines Neurobiology of the Trace Amines

Experimental and Clinical Neuroscience Neurobiology of the Trace Amines, edited by R. R. Boulton, G. B. Boker, W. G. Dewhurst, and M. Sondler, 7984

Neural Membranes, edited by Groce Y. Sun, Nicolos Bozon, long-Yen Wu, Giuseppe Parcel lot, and Rlbert Y. Sun, 7983

Experimental and Clinical Neuroscience Neurobiology of the Trace Amines, edited by R. R. Boulton, G. B. Boker, W. G. Dewhurst, and M. Sondler, 7984

Neural Membranes, edited by Groce Y. Sun, Nicolos Bozon, long-Yen Wu, Giuseppe Parcel lot, and Rlbert Y. Sun, 7983

NEUROBIOLOGY OF THE TRACE AMINES

Analytical, Physiological, Pharmacological, Behavioral, and Clinical Aspects

Edited bL,J

A. A. BOULTON, G. B. BAKER, W. G. DEWHURST, and M. SANDLER

Humana Press · Clifton, New Jersey

NEUROBIOLOGY OF THE TRACE AMINES

Analytical, Physiological, Pharmacological, Behavioral, and Clinical Aspects

Edited bL,J

A. A. BOULTON, G. B. BAKER, W. G. DEWHURST, and M. SANDLER

Humana Press · Clifton, New Jersey

Library of Congress Cataloging in Publication Data

Main entry under title:

Neurobiology of the trace amines.

"Based on the proceedings of Trace amines and the neurosciences, a meeting held at the University of Alberta, Edmonton, July 19-21, 1983 .... organized as a satellite meeting of the ninth meeting of the Internation-al Society for Neurochemistry, held in Vancouver, July 10-15, 1983"--Pref.

Includes index. 1. Biogenic amines--Congresses. 2. Neurochemistry-­

Congresses. I. Boulton, A. A. II. International Society for Neurochemistry. Meeting (9th : 1983: Vancouver, B.C.) [DNLM: I. Amines--Congresses. QU 60 N494 1983] QP80I. B66N48 1984 612' .8042 84-626 ISBN-13: 978-1-4612-9781-9 e-ISBN-13: 978-1-4612-5312-9 DOl: 10.1007/978-1-4612-5312-9

©1984 The Humana Press Inc. Crescent Manor PO Box 2148 Clifton, NJ 07015

All rights reserved.

Softcover reprint of the hardcover 1st edition 1984

No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher.

Proceedings of a meeting held at the University of Alberta, Edmonton, July 19-21, 1983.

Library of Congress Cataloging in Publication Data

Main entry under title:

Neurobiology of the trace amines.

"Based on the proceedings of Trace amines and the neurosciences, a meeting held at the University of Alberta, Edmonton, July 19-21, 1983 .... organized as a satellite meeting of the ninth meeting of the Internation-al Society for Neurochemistry, held in Vancouver, July 10-15, 1983"--Pref.

Includes index. 1. Biogenic amines--Congresses. 2. Neurochemistry-­

Congresses. I. Boulton, A. A. II. International Society for Neurochemistry. Meeting (9th : 1983: Vancouver, B.C.) [DNLM: I. Amines--Congresses. QU 60 N494 1983] QP80I. B66N48 1984 612' .8042 84-626 ISBN-13: 978-1-4612-9781-9 e-ISBN-13: 978-1-4612-5312-9 DOl: 10.1007/978-1-4612-5312-9

©1984 The Humana Press Inc. Crescent Manor PO Box 2148 Clifton, NJ 07015

All rights reserved.

Softcover reprint of the hardcover 1st edition 1984

No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher.

Proceedings of a meeting held at the University of Alberta, Edmonton, July 19-21, 1983.

PREFACE

Many of the trace amines-more correctly called biogenic amines­have been known for decades, but because of their tiny concentra­tions (0.01-100 ng/g) in brain, it was only after the development of sophisticated analytical techniques (such as mass spectrometry) that they could be identified and quantitated in nervous tissue.

There are now more than 20 of them and most are related to the catecholamines and 5-hydroxytryptamine both structurally and metabolically. Their pharmacological and physiological properties make them prime candidates for a transmitter or neuromodulator role and many of them elicit profound behavioral syndromes after injection--one of them, phenylethylamine, has even been referred to as nature's amphetamine.

In the clinical sphere several have been shown to be involved in: Parkinsonism, schizophrenia, depression, agoraphobia, aggression, hyperkinesis, migraine, hypertensive crises, hypertyrosinemia, he­patic encephalopathy, epilepsy, and cystic fibrosis. Thus the research reported here on these intriguing "new" substances will be of great interest to psychiatrists, neurologists, biochemists, pharmacologists, physiologists, psychologists, behaviorists and indeed to all those working in the neurosciences and related fields today.

PREFACE

Many of the trace amines-more correctly called biogenic amines­have been known for decades, but because of their tiny concentra­tions (0.01-100 ng/g) in brain, it was only after the development of sophisticated analytical techniques (such as mass spectrometry) that they could be identified and quantitated in nervous tissue.

There are now more than 20 of them and most are related to the catecholamines and 5-hydroxytryptamine both structurally and metabolically. Their pharmacological and physiological properties make them prime candidates for a transmitter or neuromodulator role and many of them elicit profound behavioral syndromes after injection--one of them, phenylethylamine, has even been referred to as nature's amphetamine.

In the clinical sphere several have been shown to be involved in: Parkinsonism, schizophrenia, depression, agoraphobia, aggression, hyperkinesis, migraine, hypertensive crises, hypertyrosinemia, he­patic encephalopathy, epilepsy, and cystic fibrosis. Thus the research reported here on these intriguing "new" substances will be of great interest to psychiatrists, neurologists, biochemists, pharmacologists, physiologists, psychologists, behaviorists and indeed to all those working in the neurosciences and related fields today.

ACKNOWLEDGMENTS

This book is based on the proceedings of Trace Amines and the Neurosciences, a meeting held at the University of Alberta, Edmonton, July 19-21, 1983. This meeting was organized as a Satellite Meeting of the Ninth Meeting of the International Society for Neurochemistry, held in Vancouver, July 10-15, 1983. International organizers of the satellite meeting were Drs. A. A. Boulton (Saskatoon), W. G. Dewhurst (Edmonton), G. B. Baker (Edmonton), and M. Sandler (London). Mem­bers of the local organizing committee in Edmonton were G. B. Baker, W. G. Dewhurst, M. M. Ferguson, R. T. Coutts, and R. A. Locock.

The meeting was made possible by major conference grants from the Alberta Heritage Foundation for Medical Research, the Medical Research Council of Canada, and the University of Alberta, and by grants-in-aid from (in alphabetical order) Amersham Corporation, Beckman Instruments Inc., Bristol-Myers Inc., Ciba-Geigy Canada Ltd., Hewlett-Packard (Canada) Ltd., Mandel Scientific Co. Ltd., Novopharm Ltd., Pfizer Canada Inc., Rh6ne-Poulenc Pharma Inc., Smith Kline & French Canada Ltd., SqUibb Canada Inc., Upjohn Company of Canada, and Wyeth Ltd.

We acknowledge with pleasure the presence of Dr. lionel McLeod, President of the Alberta Heritage Foundation for Medical Research, who opened the conference.

ACKNOWLEDGMENTS

This book is based on the proceedings of Trace Amines and the Neurosciences, a meeting held at the University of Alberta, Edmonton, July 19-21, 1983. This meeting was organized as a Satellite Meeting of the Ninth Meeting of the International Society for Neurochemistry, held in Vancouver, July 10-15, 1983. International organizers of the satellite meeting were Drs. A. A. Boulton (Saskatoon), W. G. Dewhurst (Edmonton), G. B. Baker (Edmonton), and M. Sandler (London). Mem­bers of the local organizing committee in Edmonton were G. B. Baker, W. G. Dewhurst, M. M. Ferguson, R. T. Coutts, and R. A. Locock.

The meeting was made possible by major conference grants from the Alberta Heritage Foundation for Medical Research, the Medical Research Council of Canada, and the University of Alberta, and by grants-in-aid from (in alphabetical order) Amersham Corporation, Beckman Instruments Inc., Bristol-Myers Inc., Ciba-Geigy Canada Ltd., Hewlett-Packard (Canada) Ltd., Mandel Scientific Co. Ltd., Novopharm Ltd., Pfizer Canada Inc., Rh6ne-Poulenc Pharma Inc., Smith Kline & French Canada Ltd., SqUibb Canada Inc., Upjohn Company of Canada, and Wyeth Ltd.

We acknowledge with pleasure the presence of Dr. lionel McLeod, President of the Alberta Heritage Foundation for Medical Research, who opened the conference.

CONTENTS

Preface... ... . ... . ... . ... ... ..... ... . ... .... ... ... . .... . .... . v Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii list of Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv

A. INTAODUOION Trace Amines: The Early Years. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 W. G. Dewhurst

Trace Amines and the Neurosciences: An Overview. . . . . . . . . . . . . . . . 13 A. A. Boulton

B. ANALYSIS Invited Communications

Quantification of Trace Amines and Their Metabolites by High Resolution or Metastable Analysis Using Double Focussing Mass Spectrometry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

D. A. Durden

The Use of Enzymatic Radioisotopic Microassays for the Quantification of ~-Phenylethylamine, Phenylethanolamine, Tyramine, and Octopamine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

J. M. Saavedra

Gas Chromatography for Analysis of the Trace Amines in Tissues and Body Fluids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

G. B. Baker, R. T. Coutts, and I. L Martin

Free Communications

Studies on Tryptamine Metabolism by GC-MS and HPLC Techniques. 71 C. Sunol, J. M. Tusell, F. Artigas, E. Martinez, A. Adell, and E. Gelpi

A Rapid and Specific Technique for the Extraction of Tyramine and .octopamine from Biological Tissues for HPLC Analysis. . . . . . . . . . 85

B. A. Bailey, A. J. Martin, and R. G. H. Downer

Analysis of Octopamine, Dopamine, 5-Hydroxtn,lptamine, and Tryptophan in the Brain and Nerve Cord of the American Cockroach. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .• . . . . . . . . . . . 91

R. J. Martin, B. A. Bailey, and R. G. H. Downer

ix

CONTENTS

Preface... ... . ... . ... . ... ... ..... ... . ... .... ... ... . .... . .... . v Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii list of Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv

A. INTAODUOION Trace Amines: The Early Years. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 W. G. Dewhurst

Trace Amines and the Neurosciences: An Overview. . . . . . . . . . . . . . . . 13 A. A. Boulton

B. ANALYSIS Invited Communications

Quantification of Trace Amines and Their Metabolites by High Resolution or Metastable Analysis Using Double Focussing Mass Spectrometry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

D. A. Durden

The Use of Enzymatic Radioisotopic Microassays for the Quantification of ~-Phenylethylamine, Phenylethanolamine, Tyramine, and Octopamine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

J. M. Saavedra

Gas Chromatography for Analysis of the Trace Amines in Tissues and Body Fluids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

G. B. Baker, R. T. Coutts, and I. L Martin

Free Communications

Studies on Tryptamine Metabolism by GC-MS and HPLC Techniques. 71 C. Sunol, J. M. Tusell, F. Artigas, E. Martinez, A. Adell, and E. Gelpi

A Rapid and Specific Technique for the Extraction of Tyramine and .octopamine from Biological Tissues for HPLC Analysis. . . . . . . . . . 85

B. A. Bailey, A. J. Martin, and R. G. H. Downer

Analysis of Octopamine, Dopamine, 5-Hydroxtn,lptamine, and Tryptophan in the Brain and Nerve Cord of the American Cockroach. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .• . . . . . . . . . . . 91

R. J. Martin, B. A. Bailey, and R. G. H. Downer

ix

x Contents

Natural Occurrence and Metabolism of the Isomeric Octopamines and Synephrines. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97

C. M. Williams, M. W. Couch, and J. M. Midgley

Octopamine is Present in Retinas of Various Mammalian Species. . .. 107 T. P. Hicks and D. Parkinson

C. PHYSIOLOGY AND PHARMACOLOGY Invited Communications

Investigation of Trace Amine Metabolism in the Central Nervous System through Measurements on Cerebrospinal Fluid. . . . . . . . .. 115

S. N. Young

Analysis of Trace Amines: Endogenous Levels and the Effects of Various Drugs on Tissue Concentrations in the Rat. . . . . . . . . . . .. 127

S. R. Philips

Drug-Induced Changes in the Central Metabolism of Tyramine and Other Trace Monoamines: Their Possible Role in Brain Functions. 145

A. V. Juorio

Aminergic Control of the Electrocorticogram: A Progress Report. . . . .. 163 C. H. Vanderwolf

Neuronal Transport of Trace Amines: An Overview. . . . . . . . . . . . . . . .. 185 L E. Dyck

Electrophysiological Studies of the Possible Role of Trace Amines in Synaptic Function. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 205

A. S. G. Jones

Effects of Octopamine and Serotonin on Neurones of Aplt,lsia Califomica . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 225

T. P. Hicks, J. P. Edstrom, and K. Lukowiak

Free Communications

Individual Housing Stress Elevates Brain and Adrenal Tryptamine Content . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 249

A. E. W. Harrison and S. T. Christian

The Uptake and Release of 14C-Tryptamine by Rat Brain Slices. . . . .. 257 L E. Dyck

Tryptamine-Induced Changes in Endogenous 5-Hydroxytryptamine and [3HI-5-HT Release from Mouse Hypothalamic Slices. . . . . . .. 265

C. M. Robinson and C. A. Marsden

Effect of Chronic Haloperidol on the Levels of Blood and Urinary Phenylethylamine and Phenylacetic Acid in Rats. . . . . . . . . . . . . .. 271

P. A. Shea, S. E. Wade, S. D. Dunlop, and H. C. Hendrie

x Contents

Natural Occurrence and Metabolism of the Isomeric Octopamines and Synephrines. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97

C. M. Williams, M. W. Couch, and J. M. Midgley

Octopamine is Present in Retinas of Various Mammalian Species. . .. 107 T. P. Hicks and D. Parkinson

C. PHYSIOLOGY AND PHARMACOLOGY Invited Communications

Investigation of Trace Amine Metabolism in the Central Nervous System through Measurements on Cerebrospinal Fluid. . . . . . . . .. 115

S. N. Young

Analysis of Trace Amines: Endogenous Levels and the Effects of Various Drugs on Tissue Concentrations in the Rat. . . . . . . . . . . .. 127

S. R. Philips

Drug-Induced Changes in the Central Metabolism of Tyramine and Other Trace Monoamines: Their Possible Role in Brain Functions. 145

A. V. Juorio

Aminergic Control of the Electrocorticogram: A Progress Report. . . . .. 163 C. H. Vanderwolf

Neuronal Transport of Trace Amines: An Overview. . . . . . . . . . . . . . . .. 185 L E. Dyck

Electrophysiological Studies of the Possible Role of Trace Amines in Synaptic Function. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 205

A. S. G. Jones

Effects of Octopamine and Serotonin on Neurones of Aplt,lsia Califomica . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 225

T. P. Hicks, J. P. Edstrom, and K. Lukowiak

Free Communications

Individual Housing Stress Elevates Brain and Adrenal Tryptamine Content . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 249

A. E. W. Harrison and S. T. Christian

The Uptake and Release of 14C-Tryptamine by Rat Brain Slices. . . . .. 257 L E. Dyck

Tryptamine-Induced Changes in Endogenous 5-Hydroxytryptamine and [3HI-5-HT Release from Mouse Hypothalamic Slices. . . . . . .. 265

C. M. Robinson and C. A. Marsden

Effect of Chronic Haloperidol on the Levels of Blood and Urinary Phenylethylamine and Phenylacetic Acid in Rats. . . . . . . . . . . . . .. 271

P. A. Shea, S. E. Wade, S. D. Dunlop, and H. C. Hendrie

Contents xi

A Comparison of Effects of Acute and Chronic Administration of Phenelzine and Tranylcypromine on Brain Concentrations of 2-Phenylethylamine, p-Tyramine, and Tryptamine in the Rat ... " 277

G. B. Saker, D. f. LeGatt, and A. T. Coutts

Phenylethylamine Deamination in the Noradrenergic Neurotransmitter System.................................................. 283

N. A. Garrick and D. L Murphy

Effect of lignocaine on Tyramine and Serotonin Oxidation in Brain. .. 291 S. J. Haque and M. K. Poddar

Degradation Kinetics by MAO of PEA Derivatives. A Model for the Molecular Basis of Their Analgesic and Behavioral Effects? ... " 299

A. D. Mosnaim, M. E. Wolf, and E. A. Zeller

The Kinetics of Hydroxylation of Phenylethylamine, Amphetamine, and Phenylalanine in Rodent Tissues. . . . . . . . . . . . . . . . . . . . . . .. 307

O. Callagahn, A. Mosnaim, J. Chevesich, and M. E. Wolf

Chronotropic and Inotropic Selectivity of Substituted Phenylethylamines in the Isolated, Perfused Rabbit Heart . . . . .. 313

D. M. ferguson and A. J. Vazquez

Trace Amine-Peptide Interactions on Central Neurones: I. Tryptamine and Substance P. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 321

R. S. G. Jones

Trace Amine-Peptide Interactions: II. Phenylethylamine and Enkephalin; p-Tyramine and Enkephalin . . . . . . . . . . . . . . . . . . . . .. 327

R. S. G. Jones

D. BEHAVIOR

Invited Communications

Beto-Phenylethylamine: Some Preliminary Chronic Studies. . . . . . . . . .. 335 D. M. Jackson and O. f. Jenkins

I3-Phenylethylamine: A Functional Role at the Behavioral Level? . . . .. 351 A. J. Greenshaw

Differentiation of Phenylethylamine (PE)- and Amphetamine (AMPH)­Induced Behaviors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 375

B. I. Diamond, A. Hitri, C. Shah, and R. L Sorison

Studies on the Mechanism of Action of I3-Phenylethylamine Stereotypy in Rodents: Implications for a I3-Phenylethylamine Animal Model of Schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 389

C. T. Dourish

Contents xi

A Comparison of Effects of Acute and Chronic Administration of Phenelzine and Tranylcypromine on Brain Concentrations of 2-Phenylethylamine, p-Tyramine, and Tryptamine in the Rat ... " 277

G. B. Saker, D. f. LeGatt, and A. T. Coutts

Phenylethylamine Deamination in the Noradrenergic Neurotransmitter System.................................................. 283

N. A. Garrick and D. L Murphy

Effect of lignocaine on Tyramine and Serotonin Oxidation in Brain. .. 291 S. J. Haque and M. K. Poddar

Degradation Kinetics by MAO of PEA Derivatives. A Model for the Molecular Basis of Their Analgesic and Behavioral Effects? ... " 299

A. D. Mosnaim, M. E. Wolf, and E. A. Zeller

The Kinetics of Hydroxylation of Phenylethylamine, Amphetamine, and Phenylalanine in Rodent Tissues. . . . . . . . . . . . . . . . . . . . . . .. 307

O. Callagahn, A. Mosnaim, J. Chevesich, and M. E. Wolf

Chronotropic and Inotropic Selectivity of Substituted Phenylethylamines in the Isolated, Perfused Rabbit Heart . . . . .. 313

D. M. ferguson and A. J. Vazquez

Trace Amine-Peptide Interactions on Central Neurones: I. Tryptamine and Substance P. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 321

R. S. G. Jones

Trace Amine-Peptide Interactions: II. Phenylethylamine and Enkephalin; p-Tyramine and Enkephalin . . . . . . . . . . . . . . . . . . . . .. 327

R. S. G. Jones

D. BEHAVIOR

Invited Communications

Beto-Phenylethylamine: Some Preliminary Chronic Studies. . . . . . . . . .. 335 D. M. Jackson and O. f. Jenkins

I3-Phenylethylamine: A Functional Role at the Behavioral Level? . . . .. 351 A. J. Greenshaw

Differentiation of Phenylethylamine (PE)- and Amphetamine (AMPH)­Induced Behaviors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 375

B. I. Diamond, A. Hitri, C. Shah, and R. L Sorison

Studies on the Mechanism of Action of I3-Phenylethylamine Stereotypy in Rodents: Implications for a I3-Phenylethylamine Animal Model of Schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 389

C. T. Dourish

xii Contents

Free Communications

Effects of Tryptamine and 5-Hydroxytryptamine on Food Intake in the Rat... . . .. . .. . . .. . .. . ... .. . .. .. . .. .. .... .. .. .. ..... .. . .. 415

C. T. Dourish and J. Broadbent

5-HT Involvement in Tryptamine-Induced Behavior in Mice. . . . . . . . . .. 423 J. Irons, C. M. Robinson, and C. A. Marsden.

Hypodipsic Effects of I3-Phenylethylamine, Phenylethanolamine, N-Methylphenylethylamine, and cJ..Amphetamine: A Temporal Analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 429

J. Broadbent, A. J. Greenshaw, and A. A. Boulton.

Taste-Dependent Effects of Low Doses of I3-Phenylethylamine and cJ..Amphetamine on Drinking in the Rat. . . . . . . . . . . . . . . . . . . . . .. 435

S. Turkish, C. T. Dourish, and S. J. Cooper.

I3-Phenylethylamine and cJ..Amphetamine: Differential Potency in the Conditioned Taste Aversion Paradigm. . . . . . . . . . . . . . . . . . . . . .. 441

A. J. Greenshaw and C. T. Dourish

Locomotor Stimulant Effect of I3-Phenylethylamine-Naloxone . . . . . . .. 449 C. T. Dourish and S. J. Cooper

E. CLINICAL STUDIES Invited Communications

The Origin, Drug Interaction, Urine, Plasma, and CSF Concentrations of Phenylacetic Acid in Normal and Psychiatric Subjects. . . . . . . . . .. 457

F. Karoum, E. F. Torrey, D. L Murphy, and R. J. Wyatt

The Catabolism of Trace Amines in Some Psychiatric Disorders. . . . .. 475 P. H. Yu, B. A. Davis, A. D. Bowen, S. Wormith, D. Addington, and A. A. Boulton

Tyramine and Depressive Illness. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 487 M. Sandler, S. M. Bonham-Carter, and P. L Walker

Phenethylamine, Tyramine, and Other Trace Amines in Patients with Affective Disorders: Associations with Clinical State and Antidepressant Drug Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 499

D. L. Murphy, F. Karoum, I. Alterman, S. lippert, and A. J. Wyatt

Phenylethylamine and Schizophrenia-Clinical and Pharmacological Results. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 515

G. P. Reynolds.

Urinary Excretion of Tryptamine in Compatison to Normetanephrine and beto-Phenylethylamine in Human Volunteers after Subchronic Treatment with Different Monoamine Oxidase Inhibitors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 525

P. R. Bieck, E. Nilsson, C. Schick, P. C. Waldmeier, and J. Lauber

xii Contents

Free Communications

Effects of Tryptamine and 5-Hydroxytryptamine on Food Intake in the Rat... . . .. . .. . . .. . .. . ... .. . .. .. . .. .. .... .. .. .. ..... .. . .. 415

C. T. Dourish and J. Broadbent

5-HT Involvement in Tryptamine-Induced Behavior in Mice. . . . . . . . . .. 423 J. Irons, C. M. Robinson, and C. A. Marsden.

Hypodipsic Effects of I3-Phenylethylamine, Phenylethanolamine, N-Methylphenylethylamine, and cJ..Amphetamine: A Temporal Analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 429

J. Broadbent, A. J. Greenshaw, and A. A. Boulton.

Taste-Dependent Effects of Low Doses of I3-Phenylethylamine and cJ..Amphetamine on Drinking in the Rat. . . . . . . . . . . . . . . . . . . . . .. 435

S. Turkish, C. T. Dourish, and S. J. Cooper.

I3-Phenylethylamine and cJ..Amphetamine: Differential Potency in the Conditioned Taste Aversion Paradigm. . . . . . . . . . . . . . . . . . . . . .. 441

A. J. Greenshaw and C. T. Dourish

Locomotor Stimulant Effect of I3-Phenylethylamine-Naloxone . . . . . . .. 449 C. T. Dourish and S. J. Cooper

E. CLINICAL STUDIES Invited Communications

The Origin, Drug Interaction, Urine, Plasma, and CSF Concentrations of Phenylacetic Acid in Normal and Psychiatric Subjects. . . . . . . . . .. 457

F. Karoum, E. F. Torrey, D. L Murphy, and R. J. Wyatt

The Catabolism of Trace Amines in Some Psychiatric Disorders. . . . .. 475 P. H. Yu, B. A. Davis, A. D. Bowen, S. Wormith, D. Addington, and A. A. Boulton

Tyramine and Depressive Illness. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 487 M. Sandler, S. M. Bonham-Carter, and P. L Walker

Phenethylamine, Tyramine, and Other Trace Amines in Patients with Affective Disorders: Associations with Clinical State and Antidepressant Drug Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 499

D. L. Murphy, F. Karoum, I. Alterman, S. lippert, and A. J. Wyatt

Phenylethylamine and Schizophrenia-Clinical and Pharmacological Results. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 515

G. P. Reynolds.

Urinary Excretion of Tryptamine in Compatison to Normetanephrine and beto-Phenylethylamine in Human Volunteers after Subchronic Treatment with Different Monoamine Oxidase Inhibitors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 525

P. R. Bieck, E. Nilsson, C. Schick, P. C. Waldmeier, and J. Lauber

Contents xiii

Free Communications

p-Hydroxyphenylacetic Acid Concentration in the CSF of Patients with Neurological and Psychiatric Disorders. . . . . . . . . . . . . . . . . . . . . .. 543

K. Kobayashi, Y. Imazu, and T. Shohmori

Noncatecholic Phenylethylamines and MAO Activity in Diabetes and Migraine... ... . ... ... ... .. . .. . ... .. .... . ... ... .... . ..... 549

A. D. Mosnaim, M. E. Wolf, and S. Diamond

Phenylethylamine and Tardive Dyskinesia. . . . . . . . . . . . . . . . . . . . . . .. 557 M. E. Wolf and A. D. Mosnaim

Phenylethylamine, Phenylacetic Acid, and Methionine Enkephalin Levels in Humans Following Profound Acute Stress. . . . . . . . . . . .. 563

M. Paulos, A. Mosnaim, M. Wolf, and A. Tessel.

14C-Tryptamine Binding in Parkinson's Disease and Hepatic Coma . .. 571 E. Kienzl, P. Riederer, K. Jellinger, and H. Noller

Biochemical'and Antidepressant Mechanisms of L-Deprenyl . . . . . . . .. 581 M. R. Uebowitz, F. Karoum, F. M. Ouitkin, J. Stewart, P. McGrath, W. Harrison, S. O. Davies, and D. F. Klein

Index....................................................... 589

Contents xiii

Free Communications

p-Hydroxyphenylacetic Acid Concentration in the CSF of Patients with Neurological and Psychiatric Disorders. . . . . . . . . . . . . . . . . . . . . .. 543

K. Kobayashi, Y. Imazu, and T. Shohmori

Noncatecholic Phenylethylamines and MAO Activity in Diabetes and Migraine... ... . ... ... ... .. . .. . ... .. .... . ... ... .... . ..... 549

A. D. Mosnaim, M. E. Wolf, and S. Diamond

Phenylethylamine and Tardive Dyskinesia. . . . . . . . . . . . . . . . . . . . . . .. 557 M. E. Wolf and A. D. Mosnaim

Phenylethylamine, Phenylacetic Acid, and Methionine Enkephalin Levels in Humans Following Profound Acute Stress. . . . . . . . . . . .. 563

M. Paulos, A. Mosnaim, M. Wolf, and A. Tessel.

14C-Tryptamine Binding in Parkinson's Disease and Hepatic Coma . .. 571 E. Kienzl, P. Riederer, K. Jellinger, and H. Noller

Biochemical'and Antidepressant Mechanisms of L-Deprenyl . . . . . . . .. 581 M. R. Uebowitz, F. Karoum, F. M. Ouitkin, J. Stewart, P. McGrath, W. Harrison, S. O. Davies, and D. F. Klein

Index....................................................... 589

CONTRIBUTORS

D. ADDINGTON· Regional Psychiatric Center, Saskatoon, Sas­katchewan, Canada

A. ADELL • Instituto de Quimica Bio-Organica, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain

I. ALTERMAN· National Institute of Mental Health, Bethesda, Maryland

**F. ARTIGAS • Instituto de Quimica Bio-Organica, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain

B. A. BAILEY • Department of Biology, University of Waterloo, Water­loo, Ontario, Canada

*G. B. BAKER • Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada

*P. R. BlECK • Human Pharmacology Institute, CIBA-GEIGY GmBH, Tuebingen, Federal Republic of Germany

S. M. BONHAM-CARTER • The Bernhard Baron Memorial Research Lab­oratories and Institute of Obstetrics and Gynaecology, Queen Charlotte's Maternity Hospital, London, England

R. L. BORISON • Department of Psychiatry, Medical College of Georgia and Augusta V. A. Medical Center, Augusta, Georgia

*A. A. BOULTON· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Sakastchewan, Canada

R. BOWEN • Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

J. BROADBENT· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

**0. H. CALLAGHAN • Department of Biochemistry, Chicago Medical School, University of Health Sciences, North Chicago, Illinois

xv

CONTRIBUTORS

D. ADDINGTON· Regional Psychiatric Center, Saskatoon, Sas­katchewan, Canada

A. ADELL • Instituto de Quimica Bio-Organica, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain

I. ALTERMAN· National Institute of Mental Health, Bethesda, Maryland

**F. ARTIGAS • Instituto de Quimica Bio-Organica, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain

B. A. BAILEY • Department of Biology, University of Waterloo, Water­loo, Ontario, Canada

*G. B. BAKER • Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada

*P. R. BlECK • Human Pharmacology Institute, CIBA-GEIGY GmBH, Tuebingen, Federal Republic of Germany

S. M. BONHAM-CARTER • The Bernhard Baron Memorial Research Lab­oratories and Institute of Obstetrics and Gynaecology, Queen Charlotte's Maternity Hospital, London, England

R. L. BORISON • Department of Psychiatry, Medical College of Georgia and Augusta V. A. Medical Center, Augusta, Georgia

*A. A. BOULTON· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Sakastchewan, Canada

R. BOWEN • Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

J. BROADBENT· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

**0. H. CALLAGHAN • Department of Biochemistry, Chicago Medical School, University of Health Sciences, North Chicago, Illinois

xv

xvi

J. CHEVESICH • Department of Biochemistry, Chicago Medical School. University of Health Sciences, North Chicago, Illinois

S. T. CHRISTIAN • Neurosciences Program, University of Alabama in Birmingham, Birmingham, Alabama

**S. J. COOPER· Department of Psychology, University of Birmingham, Birmingham, England

A. T. couns • Neurochemical Research Unit, University of Alberta, Edmonton, Alberta, Canada

M. W. COUCH • Veterans Administration Medical Center and Depart­ment of Radiology, University of Florida College of Medicine, Gainesville, Florida

S. O. DAVIES • New York State Psychiatric Institute, New York, NY

B. A. DAVIS· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

*W. G. DEWHURST • Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada

*B. I. DIAMOND • Department of Psychiatry, Medical College of Georgia and Augusta V. A. Medical Center, Augusta, Georgia

S. DIAMOND • Diamond Headache Clinic, Chicago, Illinois

*c. T. DOURISH· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

**A. G. H. DOWNER • Department of Biology, University of Waterloo, Waterloo, Ontario, Canada

S. D. DUNLOP • Institute of Psychiatric Research, Department of Psy­chiat"" Indiana University School of Medicine, Indianapolis, Indiana

*0. A. DURDEN· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

*l. E. DYCK· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

J. P. EDSTROM • Department of Medical Physiology, University of Calgary, Calga"" Alberta, Canada

**D. M. FERGUSON • Department of Pharmacology, University of Health Sciences, The Chicago Medical School, North Chicago, Illinois

N. A. GARRICK • Clinical Neuropharmacology Branch, National Insti­tute of Mental Health, Bethesda, Maryland

xvi

J. CHEVESICH • Department of Biochemistry, Chicago Medical School. University of Health Sciences, North Chicago, Illinois

S. T. CHRISTIAN • Neurosciences Program, University of Alabama in Birmingham, Birmingham, Alabama

**S. J. COOPER· Department of Psychology, University of Birmingham, Birmingham, England

A. T. couns • Neurochemical Research Unit, University of Alberta, Edmonton, Alberta, Canada

M. W. COUCH • Veterans Administration Medical Center and Depart­ment of Radiology, University of Florida College of Medicine, Gainesville, Florida

S. O. DAVIES • New York State Psychiatric Institute, New York, NY

B. A. DAVIS· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

*W. G. DEWHURST • Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada

*B. I. DIAMOND • Department of Psychiatry, Medical College of Georgia and Augusta V. A. Medical Center, Augusta, Georgia

S. DIAMOND • Diamond Headache Clinic, Chicago, Illinois

*c. T. DOURISH· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

**A. G. H. DOWNER • Department of Biology, University of Waterloo, Waterloo, Ontario, Canada

S. D. DUNLOP • Institute of Psychiatric Research, Department of Psy­chiat"" Indiana University School of Medicine, Indianapolis, Indiana

*0. A. DURDEN· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

*l. E. DYCK· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

J. P. EDSTROM • Department of Medical Physiology, University of Calgary, Calga"" Alberta, Canada

**D. M. FERGUSON • Department of Pharmacology, University of Health Sciences, The Chicago Medical School, North Chicago, Illinois

N. A. GARRICK • Clinical Neuropharmacology Branch, National Insti­tute of Mental Health, Bethesda, Maryland

xvii

E. GelPi • Instituto de Quimica Bio-Organica, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain

*A. J. GAEENSHAW • Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

S. J. HAQUE • Department of Biochemistry, University of Calcutta, Calcutta, India

**R. E. W. HARRISON • Department of Physiology, Rush Medical College, Chicago, Illinois

W. HARAlSON • Depression Evaluation Services, New York State Psy­chiatric Institute, New York, NY

H. C. HENDRIE • Institute of Psychiatric Research, Department of Psy­chiatry, Indiana University School of Medicine, Indianapolis, Indiana

*1. P. HICKS • Department of Medical Physiology and Anatomy, Uni­versity of Calgary, Calgary, Alberta, Canada

A. HllRI • Department of Psychiatry, Medical College of Georgia and Augusta V. A. Medical Center, Augusta, Georgia

Y. IMAZU • Department of Clinical Neurochemistry, Okayama Univer­sity Medical School. Shikata-cho, Okayama, Japan

J. IRONS • Department of Physiology and Pharmacology, Queen's Medical Centre, Nottingham, England

*D. M. JACKSON • Department of Pharmacology, University of Sydney, Sydney, New South Wales, Australia

K. JELLINGER • LudWig Boltzmann Institut fur Klinische Neurobiologie, Krankenhaus Wein-Laing, Wien, Austria

O. F. JENKINS • Department of Pharmacology, University of Sydney, Sydney, New South Wales, Australia

R. S. G. JONES • Biology Research Laboratories, ClBA-GEIGY AG, Basle, Sw i tzerland

*A. V. JUORIO· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

*F. KAROUM • National Institute of Mental Health Research, St. Elizabeth's Hospital, Washington,~ DC

*E. KIENZL • LudWig Boltzmann Institut fur Klinische Neurobiologie, Arbeitsgruppe Neurochemie, Krankenhaus Wein-Laing, Wien, Austria

D. F. KLEIN • New York State Psychiatric Institute, New York, NY

xvii

E. GelPi • Instituto de Quimica Bio-Organica, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain

*A. J. GAEENSHAW • Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

S. J. HAQUE • Department of Biochemistry, University of Calcutta, Calcutta, India

**R. E. W. HARRISON • Department of Physiology, Rush Medical College, Chicago, Illinois

W. HARAlSON • Depression Evaluation Services, New York State Psy­chiatric Institute, New York, NY

H. C. HENDRIE • Institute of Psychiatric Research, Department of Psy­chiatry, Indiana University School of Medicine, Indianapolis, Indiana

*1. P. HICKS • Department of Medical Physiology and Anatomy, Uni­versity of Calgary, Calgary, Alberta, Canada

A. HllRI • Department of Psychiatry, Medical College of Georgia and Augusta V. A. Medical Center, Augusta, Georgia

Y. IMAZU • Department of Clinical Neurochemistry, Okayama Univer­sity Medical School. Shikata-cho, Okayama, Japan

J. IRONS • Department of Physiology and Pharmacology, Queen's Medical Centre, Nottingham, England

*D. M. JACKSON • Department of Pharmacology, University of Sydney, Sydney, New South Wales, Australia

K. JELLINGER • LudWig Boltzmann Institut fur Klinische Neurobiologie, Krankenhaus Wein-Laing, Wien, Austria

O. F. JENKINS • Department of Pharmacology, University of Sydney, Sydney, New South Wales, Australia

R. S. G. JONES • Biology Research Laboratories, ClBA-GEIGY AG, Basle, Sw i tzerland

*A. V. JUORIO· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

*F. KAROUM • National Institute of Mental Health Research, St. Elizabeth's Hospital, Washington,~ DC

*E. KIENZL • LudWig Boltzmann Institut fur Klinische Neurobiologie, Arbeitsgruppe Neurochemie, Krankenhaus Wein-Laing, Wien, Austria

D. F. KLEIN • New York State Psychiatric Institute, New York, NY

xviii

**K. KOBAYASHI • Department of Clinical Neurochemistry, Institute for Neurobiology, Okayama University Medical School, Shikata-cho, Okayama, Japan

J. lAUBEA· Research Department, CIBA-GEIGY ltd., Basle, Switzerland

D. F. leGATT • Department of laboratory Medicine, University of Alberta Hospital, Edmonton, Alberta, Canada

M. A. LIEBOWITZ • Anxiety Disorders Clinic, New York State Psychiatric Institute, New York, NY

S. LIPPER • National Institute of Mental Health, Bethesda, Maryland

K. LUKOWIAK • Department of Medical Physiology, University of Calgary, Calgary, Alberta, Canada

**c. A. MARSDEN • Department of Physiology and Pharmacology, Queen's Medical Centre, Nottingham, England

I. L MARTIN • MRC Neurochemical Pharmacology Unit, Medical Re­search Council Centre, Cambridge, England

A. J. MARTIN • Department of Biology, University of Waterloo, Water­loo, OntariO, Canada

E. MAATINEZ • Instituto de Quimica Bio-Organica, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain

P. McGRATH • New York State Psychiatric Institute, New York, NY

J. M. MIDGElEY • School of Pharmacy, University of london, london, England

*A. D. MOSNAIM • Department of Pharmacology, University of Health Sciences, The Chicago Medical School, North Chicago, Illinois

*D. L MURPHY • Clinical Neuropharmacology Branch, National Insti­tute of Mental Health, Bethesda, Maryland

E. NILSSON • Human Pharmacology Institute, CIBA-GEIGY GmbH, Tuebingen, Federal Republic of Germany

H. NOllER • Institute for Physical Chemistry, Technical University, Vienna, Austria

D. PARKINSON • Department of Medical Physiology, Faculty of Medi­cine, University of Calgary, Calgan," Alberta Canada

**M. PAULOS • DuPont Co., Wilmington, Delaware

*S. A. PHILIPS· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

**M. K. PODDAR • Department of Biochemistry, University of Calcutta, Calcutta, India

xviii

**K. KOBAYASHI • Department of Clinical Neurochemistry, Institute for Neurobiology, Okayama University Medical School, Shikata-cho, Okayama, Japan

J. lAUBEA· Research Department, CIBA-GEIGY ltd., Basle, Switzerland

D. F. leGATT • Department of laboratory Medicine, University of Alberta Hospital, Edmonton, Alberta, Canada

M. A. LIEBOWITZ • Anxiety Disorders Clinic, New York State Psychiatric Institute, New York, NY

S. LIPPER • National Institute of Mental Health, Bethesda, Maryland

K. LUKOWIAK • Department of Medical Physiology, University of Calgary, Calgary, Alberta, Canada

**c. A. MARSDEN • Department of Physiology and Pharmacology, Queen's Medical Centre, Nottingham, England

I. L MARTIN • MRC Neurochemical Pharmacology Unit, Medical Re­search Council Centre, Cambridge, England

A. J. MARTIN • Department of Biology, University of Waterloo, Water­loo, OntariO, Canada

E. MAATINEZ • Instituto de Quimica Bio-Organica, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain

P. McGRATH • New York State Psychiatric Institute, New York, NY

J. M. MIDGElEY • School of Pharmacy, University of london, london, England

*A. D. MOSNAIM • Department of Pharmacology, University of Health Sciences, The Chicago Medical School, North Chicago, Illinois

*D. L MURPHY • Clinical Neuropharmacology Branch, National Insti­tute of Mental Health, Bethesda, Maryland

E. NILSSON • Human Pharmacology Institute, CIBA-GEIGY GmbH, Tuebingen, Federal Republic of Germany

H. NOllER • Institute for Physical Chemistry, Technical University, Vienna, Austria

D. PARKINSON • Department of Medical Physiology, Faculty of Medi­cine, University of Calgary, Calgan," Alberta Canada

**M. PAULOS • DuPont Co., Wilmington, Delaware

*S. A. PHILIPS· Psychiatric Research Division, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

**M. K. PODDAR • Department of Biochemistry, University of Calcutta, Calcutta, India

xix

F. M. QUITKIN • Depression Evaluation Service, New York State Psy­chiatric Institute, New York, NY

*G. P. REYNOLDS • Department of Neurological Surgery and Neurol­ogy, Addenbrooke's Hospital, Cambridge, England

P. RIEDERER • Ludwig Boltzmann Institut fur Klinische Neurobiologie, Arbeitsgruppe Neurochemie, Krankenhaus Wien-Laing, Wien, Austria

C. M. ROBINSON • Department of Physiology and Pharmacology, Queen's Medical Centre, Nottingham, England

*J. M. SAAVEDRA • Section on Pharmacology, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland

*M. SANDLER • The Bernhard Baron Memorial Research, Laboratories and Institute of Obstetrics and Gynaecology, Queen Charlotte's Maternity Hospital, London, England

C. SCHICK· Human Pharmacology Institute, ClBA-GEIGY GmbH, Tuebingen, Federal Republic of Germany

C. SHAH • Department of Psychiatry and Augusta V. A. Medical Center, Augusta, Georgia

**P. A. SHEA • Institute of Psychiatric Research, Department of Psychi­atry, Indiana University School of Medicine, Indianapolis, Indiana

T. SHOHMORI • Department of Clinical Neurochemistry, Institute for Neurobiology, Okayama University Medical School, Shikata-cho, Okayama Japan

J. STEWART • Anxiety Disorders Clinic, New York State Psychiatric In­stitute, New York, NY

C. SUNOL • Instituto de Quimica Bio-Organica, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain

A. E. TESSEL • Department of Pharmacology and Toxicology, University of Kansas, Lawrence, Kansas

E. F. TORREY • National Institute of Mental Health Research, St. Elizabeth's Hospital, WAW Building, Washington, DC

S. TURKISH • Department of Psychology, University of Birmingham, Birmingham, England

J. M. TUSSELL • Instituto de Quimica Bio-Organica, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain

*c. H. VANDERWOLF • Department of Psychology, University of West­ern Ontario, London, OntariO. Canada

xix

F. M. QUITKIN • Depression Evaluation Service, New York State Psy­chiatric Institute, New York, NY

*G. P. REYNOLDS • Department of Neurological Surgery and Neurol­ogy, Addenbrooke's Hospital, Cambridge, England

P. RIEDERER • Ludwig Boltzmann Institut fur Klinische Neurobiologie, Arbeitsgruppe Neurochemie, Krankenhaus Wien-Laing, Wien, Austria

C. M. ROBINSON • Department of Physiology and Pharmacology, Queen's Medical Centre, Nottingham, England

*J. M. SAAVEDRA • Section on Pharmacology, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland

*M. SANDLER • The Bernhard Baron Memorial Research, Laboratories and Institute of Obstetrics and Gynaecology, Queen Charlotte's Maternity Hospital, London, England

C. SCHICK· Human Pharmacology Institute, ClBA-GEIGY GmbH, Tuebingen, Federal Republic of Germany

C. SHAH • Department of Psychiatry and Augusta V. A. Medical Center, Augusta, Georgia

**P. A. SHEA • Institute of Psychiatric Research, Department of Psychi­atry, Indiana University School of Medicine, Indianapolis, Indiana

T. SHOHMORI • Department of Clinical Neurochemistry, Institute for Neurobiology, Okayama University Medical School, Shikata-cho, Okayama Japan

J. STEWART • Anxiety Disorders Clinic, New York State Psychiatric In­stitute, New York, NY

C. SUNOL • Instituto de Quimica Bio-Organica, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain

A. E. TESSEL • Department of Pharmacology and Toxicology, University of Kansas, Lawrence, Kansas

E. F. TORREY • National Institute of Mental Health Research, St. Elizabeth's Hospital, WAW Building, Washington, DC

S. TURKISH • Department of Psychology, University of Birmingham, Birmingham, England

J. M. TUSSELL • Instituto de Quimica Bio-Organica, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain

*c. H. VANDERWOLF • Department of Psychology, University of West­ern Ontario, London, OntariO. Canada

xx

A. J. VAZQUEZ • Department of Pharmacology, University of Health Sciences, The Chicago Medical School, North Chicago, Illinois

S. E. WADE • Institute of Psychiatric Aesearch, Department of Psychia­try, Indiana University School of Medicine, Indianapolis, Indiana

P. C. WALDMEIEA • Pharmaceuticals Division, CIBA-GEIGY Ltd., Basle, Switzerland

P. l. WALKEA • The Bernhard Baron Memorial Aesearch Laboratories and Institute of Obstetrics and Gynaecology, Queen Charlotte's Maternity Hosptial, London, England

**c. M. WILLIAMS • Veterans Administration Medical Center and De­partment of Aadiology, University of Florida College of Medicine Gainesville, Florida

**M. E. WOLF • Tardive Dyskinesia Program, Veterans Administration Medical Center, North Chicago, Illinois

S. WOAMITH· Aegional Psychiatric Center, Saskatoon, Saskatchewan, Canada

A. J. WYATI • National Institute of Mental Health Aesearch, Saint Elizabeth's Hospital, WAW Building, Washington, DC

*S. N. YOUNG· Department of Psychiatry, McGill University, Montreal, Quebec Canada

*P. H. YU • Cancer and Medical Aesearch Building, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

E. A. ZELLEA • Chicago Medical School and Shriners Hospital, North Chicago, Illinois

* = Principal author, invited lecture ** = Principal author, free communication

xx

A. J. VAZQUEZ • Department of Pharmacology, University of Health Sciences, The Chicago Medical School, North Chicago, Illinois

S. E. WADE • Institute of Psychiatric Aesearch, Department of Psychia­try, Indiana University School of Medicine, Indianapolis, Indiana

P. C. WALDMEIEA • Pharmaceuticals Division, CIBA-GEIGY Ltd., Basle, Switzerland

P. l. WALKEA • The Bernhard Baron Memorial Aesearch Laboratories and Institute of Obstetrics and Gynaecology, Queen Charlotte's Maternity Hosptial, London, England

**c. M. WILLIAMS • Veterans Administration Medical Center and De­partment of Aadiology, University of Florida College of Medicine Gainesville, Florida

**M. E. WOLF • Tardive Dyskinesia Program, Veterans Administration Medical Center, North Chicago, Illinois

S. WOAMITH· Aegional Psychiatric Center, Saskatoon, Saskatchewan, Canada

A. J. WYATI • National Institute of Mental Health Aesearch, Saint Elizabeth's Hospital, WAW Building, Washington, DC

*S. N. YOUNG· Department of Psychiatry, McGill University, Montreal, Quebec Canada

*P. H. YU • Cancer and Medical Aesearch Building, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

E. A. ZELLEA • Chicago Medical School and Shriners Hospital, North Chicago, Illinois

* = Principal author, invited lecture ** = Principal author, free communication