SEROTONIN FROM CELL B,OLOGY TO PHARMACOLOGY

AND THERAPEUTICS

SEROTONIN

FROM CEll BIOLOGY TO PHARMACOLOGY AND THERAPEUTICS

Edited by

RODOLFO PAOLETII

Fondazione Lorenzini, Milan, Italy

PAUL M. VANHOUTTE

Mayo Clinic, Rochester, Minnesota, US.A.

NICOLETIA BRUNELLO

Institute of Pharmacological Sciences, University of Milan, Italy

and

FRANCO M. MAGGI

Institute of Pharmacological Sciences, University of Milan, Italy

.. KLUWER ACADEMIC PUBLISHERS DORDRECHT / BOSTON / LONDON

Library of Congress Cataloging in Publication Data

Serotenln f rol cell biology to.pharucology ~nd therapeutics I ed ite d by Paul M. Vanhou tte and ROdolfo Paolett I.

p. cn . "Proceedings of the Invi ted lectures ef the FirSt Internationa l

SYlposlul on "Serotonin fro. Cell Biology t o Pharucology a nd Th e r ape utiCS" IIh leh il lS held In F l orence on Ma rch 29-Aprll I , 1989"­- Pref.

ISBN 0-7923-053 1-0 (U.S.) I. SerO tOntn--Physlo logl cal e ffe ct--Congre sses. 2. Serotonln ­

-Receptors--Congruses. I . Vanhoutte. Plul M. II. Plolett l . !'Iodolfo. Ill. Internatlon~1 SYI PO S 1UI on ' SerOTOnln fron Cell BIology to Pharneology and The rapautlcs" 11$ t 1989 Florence, Italy)

IOM..M : I. SerOTonln--pharucology--cengresses. 2. SerOTon ln--physlology--congresses. av 126 S48S2 1989J CP80 1.S4S4731989 612.0157--dc20 OM..MfOLC for Library of Congress 89-24584

ISBN-13 : 978-94-0 10-7353-0 DOl: 10 . 1007/978-9 4-009- 1912-9

9-ISBN-13: 978-9 4-009- 1912-9

Published by Kluwer Academic Publishers, P.O. Box 17, 3300 AA Dordrecht. The Netherlands.

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CON1RIBUTORS LIST

George K. Aghajanian, Yale University, School of Medicine, Department of Psychiatry and Mental Health Center, 34 Park Street, NEW HAYEN Connecticut 06508, USA

Maria Luisa Barbaccia, Dipartimento di Medicina Sperimentale, e Scienze Biomediche, Universita' Tor Vergata, Via Orazio Raimondo, 00 173 ROME, Italy

K. Bech, Dept. of Surgical Gastroenterology, Odense University Hospital, DK-5000 ODENSE C, Denmark

R. Blois, Clin. Bel Air, 8 Chemin Petit-Bel-Air, CH-1225 CHENE-BOURG Geneve, Switzerland

John E. Blundell, Department of Psychology, University of Leeds, LEEDS L82 9JT, UK

Susan-Lynn Brown, Albert Einstein College of, Medicine of Yeshiva Univ. Montefiore Medical Center, 1300 Morris Park Avenue, BRONX New York 10461, USA

Nicoletta Brunello, Istituto di Scienze Farmacologiche, Via Balzaretti 9, 20133 MILAN, Italy

Giovanni B. Cassano, ClinicaPsichiatrica, Universita' di Pisa, Via Roma 67,56100 PISA, Italy

Jay D. Coffman, Professor of Medicine, University Hospital, 75 East Newton Street, BOSTON MA 02118, USA

Marlene L. Cohen, Dept. of Cardiovascular, Pharmacology, Lilly Research Laboratories, 307 East Mc Carty Street, INDIANAPOLIS - IN 46285, USA

P.J. Cowen, Oxford University, Dept. of Psychiatry, and MRC Clin. Pharmacology Unit, Research Unit, Littlemore Hospital, OXFORD OX4 4NX, UK

S. Cullheim, Department of Anatomy, Karolinska Institutet, Box 60400, S-10401 STOCKHOLM, Sweden

J.F.W. Deakin, Senior Lecturer in Psychiatry, University of Manchester, Department of Psychiatry, University Hospital of South-West, Didsbury, MANCHESTER M20 8LR, UK

D. de Chaffoy de Courcelles, Dept. of Biochemistry, Division of, Janssen Pharmaceutica N.V. Turnhout­seweg 30, B-2340 BEERSE, Belgium

Fred de Clerck, Dept. Haematology, Janssen Research Foundation, Div. of Janssen Pharmaceutica N.V. Tumhoutseweg 30, B-2340 BEERSE, Belgium

Claude De Montigny, Department of Psychiatry, McGill University, 1033 Pine Ave West, Rm. 209, MONTREAL (Quebec) H3A 1A1, Canada

Errol B. De Souza, National Research Center, on Drug Abuse, Addiction Research Center, P.O. Box 5180, BALTIMORE MD 21224, USA

v

vi

Paolo Falaschi, Clinica Medica V, Universita' "La Sapienza", Pole Aldo Moro, 00135 ROME, Italy

A. Fargin, Department of Physiology, Duke University, Medical Center, P.O. Box 3287, DURHAM N.C. 27710, USA

John R. Fozard, Sandoz Ltd. Pharma Division, Preclinical Research, Ch-4002 BASLE, Switzerland

Ray W. Fuller, Research Advisor, Lilly Research Laboratories, Lilly Corporate Center, INDIANAPOLIS IN 46285, USA

Kjell Fuxe, Karolinska Institutet, Department of Histology, P.O. Box 60400, S-I04 01 STOCKHOLM, Sweden

Silvio Garattini, Direttore, Istituto di Ricerche, Farmacologiche "Mario Negri", Via Eritrea 62, 20157 MILAN, Italy

Michael Gershon, Dept. of Anat. and Cell BioI. Columbia University, College of Physicians and, Surgeons, 630 West 168th Street, NEW YORK NY 10032, USA

Richard A. Glennon, Medical College of Virginia, Virginia Commowealth Univ. Dept. of Medicinal Chemistry, P.O. Box 581, RICHMOND Virginia 23298-0581, USA

M. Gothert, Institut fur Pharmakologie, und Toxicologie, der Universitat Bonn, Reuterstrasse 2b, 5300 BONNl,FRG

Gary A. Gudelsky, Dept. Psychiatry, Case Western Reserve Univ. Hanna Pavilion, 2040 Abington Rd. CLEVELAND OH 44106, USA

Michel Hamon, Institut National de la, Sante et de Recherche Medicale, INSERM U. 228, Fac. de Med. Pitie-Salpetriere, 91 Boulevard de I'Hospital, 75634 PARIS Cedex 13, France

Paul Hartig, Neurogenetic Corporation, 215 College Road, PARAMUS NJ 07562, USA

Donald D. Heistad, Cardiovascular Center, University of Iowa and, Veterans Administration Hospital, IOWA CITY IA 52242, USA

George R. Heninger, Dept. Psychiatry, Yale Univ. Medical School, 34 Park St. NEW HAVEN CT 06519, USA

John Hyttel, Department of Pharmacology, and Toxicology, H. Lundbeck AlS, Ottiliavej 7-9, DK-2500 COPENHAGEN Valby, Denmark

Bernard M. Jaffe, Department of Surgery, State Univ. of New York, Health Science, Center at Brooklyn, 450 Clarkson Avenue Box 40, BROOKLYN NY 11203, USA

W. Janssens, Janssen Pharmaceutica, Tumhoutseweg 30, B-2340 BEERSE, Belgium

vii

AJ. Kaumann, Associate Director Pharmacology, Smith Kline and French Res. Ltd. The Fry the, WEL­WYN Hertfordshire AL6 9AR, UK

G.J. Kilpatrick, Glaxo Group Res. Limited, Neuropharmacology Dept. WARE Hertfordshire SG12 ODJ, UK

S.Z. Langer, Lab. d'Etudes et de, Recherches Synthelabo, Dept. de Recherche, Biologique, 58 Rue de la Glaciere, 75013 PARIS, France

M. Lapiere, Centre Hospitalier, Universitaire de Liege, Service de Dermatologie, Boulevard de la Costitu­tion 66, 4020 LIEGE 1, Belgium

P.D. Leathwood, Nestec Ltd. Nestle Research Lab. 55 Ave Nestle, CH-18oo VEVEY, Switzerland

D. Lebrec, Institut National, de la Sante, INSERM U24, Hopital Beaujon, 100 BI du General-Leclerc, F-92118 CLICHY Cedex, France

Sarah F. Leibowitz, The Rockefeller University, Dept. Neuropharmacology, 1230 York Avenue, NEW YORK 10021-6399, USA

J. Leysen, Janssen Pharmaceutical, Research Laboratories, Turnhouseweg 30, B-2340 BEERSE, Belgium

Stanley A. Lorens, Department of Pharmacology, Building 135, Loyola University, Medical Center, 2160 South First Avenue, MAYWOOD IL 60153, USA

Saul Maayani, Department of Pharmacology, Mount Sinai, School of Medicine, Box 1215, One Gustave L. Levy Place, NEW YORK NY 10029, USA

J. Mendlewicz, Universite Libre de Bruxelles, Hospital Erasme, Service de Psychiatrie, Route de Lennik 808, B-1070 BRUXELLES, Belgium

D.N. Middlemiss, Biochemistry Department, Merck Sharp & Dohme Res. Lab. Neuroscience Research Centre, Terlings Park Eastwick Road, HARLOW Essex CM20 2QR, UK

Dennis L. Murphy, Chief Lab. Clinical Science, NIMH - IRP, NIH Clinical Center, 9000 Rockville Pike, BETHESDA MD 20892, USA

David L. Nelson, The University of Arizona, College of Pharmacy, Dept. of Pharmacology and, Toxicol­ogy, TUCSON Arizona 85721, USA

C. Niemegeers, Janssen Research Council, Janssen Pharmaceutica N.V. Turnhoutseweg 30, B-2340 BEERSE, Belgium

Christer Owman, University of Lund, Dept. of Medical Cell

J.M. Palacios, Sandoz Ltd. Pharmaceutical Division, Preclinical Research, CH-4002 BASLE, Switzerland

Vlll

Stephen J. Peroutka, Stanford Univ. Medical Center, Department of Neurology, STANFORD California 94305-52305, USA

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Paolo Preziosi, Istituto di Farmacologia, Universita' Cattolica, del Sacro Cuore, Largo Vito 1, 00168 ROME, Italy

Maurizio Raiteri, Universita' di Genova, Istituto di Farmacologia, e Farmacognosia, Viale Cembrano 4, 16148 GENOA, Italy

B. Richardson, Pharmaceutical Division, Preclinical Research, Sandoz Ltd. CH-4002 BASLE, Switzerland

Marco Riva, Center for Molecular and, Behavioral Neurosciences, Rutgers University, 195 University Avenue, NEWARK NJ 07102, USA

J.I.S. Robertson, Janssen Research Foundation, Division of Janssen, Pharmaceutica N.V. Tumhoutseweg 30, B-2340 BEERSE, Belgium

R. Rooman, Dept. Cellular Biology and, Pathology, Janssen Research Foundation, Div. of Janssen Pharm. N.V. Turnhoutseweg 30, B-2340 BEERSE, Belgium

Bryan L. Roth, Department of Psychiatry, Rm S-253, Stanford Univ. Medical Center, STANFORD CA 94305, USA

Neil E. Rowland, Department of Psychology, University of Florida, GAINESVILLE Florida 32611, USA

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Elaine Sanders-Bush, Howard Hughes Medical, Institute at Nashville, Vanderbilt Univ. School of Med. Rudolph Light Hall Room 702, NASHVILLE Tennessee 37232, USA

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Pramod Saxena, Erasmus Universiteit Rotterdam, Faculteit der Geneeskunde, Molewaterp1ein 50, 3000 ROTTERDAM, The Netherlands

Lewis S. Seiden, Dept. of Pharmacological, and Physiological Sciences, University of Chicago, 947 East 58th Street, CHICAGO IL60637, USA

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ix

Hiroaki Shimokawa, Dept. of Internal Medicine, Cardiovascular Center Room E316-1, University of Iowa, IOWA CITY IA 52242, USA

Federigo Sicuteri, Clinica Medica IV, Universita' di Firenze, Viale Morgagni 85, 50134 FLORENCE, Italy

J. Traber, Troponwerke GmbH & Co. KG, Postfach 801060, Berliner Strasse 156, D-5000 KOLN 80, FRG

Louis Van de Kar, Dept. Pharmacology, Loyola University, Stritch School of Medicine, 2160 South First Avenue, MAYWOOD IL60153, USA

P.M. Vanhoutte, Mayo Clinic, Medical School, Dept. of Physiology, and Biophysics, ROCHESTER MN 55905, USA

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Robert Walker, The University of Southampton, School of Biochemical and, Physiological Sciences, Med. & Biological Sciences Bldg. Bassett Crescent East, SOUTHAMPTON S09 3TU, UK

A. Wauquier, Dept. Neuropsychopharmacology, Janssen Research Foundation, Division of Janssen, Pharmaceutica N.V. Tumhoutseweg 30, B-2340 BEERSE, Belgium

J.D. Wood, The Ohio State University, Department of Physiology, 4196 Graves Hall, 333 West 10th Avenue, COLUMBUS OH4321O-1239, USA

Richard J. Wurtrnan, Massachusetts Inst. of Technology, Department of Brain and, Cognitive Sciences, Room E25-604, CAMBRIDGE Massachusetts 02139, USA

Maurice M. Rapport, Albert Einstein College of Medicine, 1300 Morris Park Ave. F-316, BRONX New York 10461, USA

PREFACE

This volume represents the proceedings ofthe invited lectures ofthe first International Symposium on "Serotonin from Cell Biology to Pharmacology and Therapeutics" which was held in Florence on March 29 - Aprill, 1989. This meeting, held under the co-sponsorship of the Serotonin Club and the Fondazione Giovanni Lorenzini, represents the first attempt to bring together scientists fascinated by the complexity of the action of 5-hydroxytryptamine throughout the body and in various species. Hence this volume provides the reader with the unique overview of the sources, effects, receptors, physiological actions and pathological role of Serotonin. As such it will be of interest not only to the person devoting herorhis research efforts to the study of 5-hydroxytryptamine but also to all scholars and even clinicians wanting to know how the powerful monoamine can modulate cellular functions. To accelerate the publication of these proceedings the Editors and the publishers have selected the camera ready format and have avoided a lengthy refereeing process. Hence the scientific content of, and the opinions expressed in the chapters are the sole responsibility of the authors.

The Editors Milan and Houston

The Editors want to thank Mrs. H. Liepman and her staff at Kluwer for the prompt and efficient handling of the manuscripts.

xi

TABLE OF CONTENTS

Contributors list v

Preface xi

M.M. RAPPORT: Serotonin research: historical overview

MOLECULAR MECHANISMS IN SEROTONIN MEDIATED RESPONSE 5

HARTIGP.R

HAMONM. Co-authors

FARGIN A.

Co-authors

DE CHAFFOY DE COURCELLES D. Co-author

ROTH B.L.

MAAYANIS. Co-author

LANGERS.Z. Co-authors

SHIRJ.C.

Co-author

Molecular biology of the serotonin receptor family 7

Molecular structure of the central 5-HT1A receptor 13 El Mestikawy S., Emerit M.B. and Gozlan H.

Biochemical characterization of the cloned human 5-HT IA receptor expressed in mammalian cells 19 Raymond J.R., Lefkowitz RJ. and Caron M.G.

Amplifying effects of 5-hydroxytryptamine on human platelets and signal transduction 25 DeClerckF.

Role of phosphoinositide hydrolysis and protein kinase C activation in 5HTz receptor function in smooth muscle 33

Adenylate cyclase-linked 5-hydroxytryptamine receptors in the brain Sherman M.R 39

Characterization and purification of the neuronal5-HT transporter 53 Lee C.R, Esnaud H. and Graham D.

Structure and functional expression of cloned human liver MAO A and B 61 Lan N.C.

PHYSIOLOGY OF SEROTONERGIC SYSTEM:

- Vascular System:

JANSSENS W.J. Co-author

DECLERCKF. Co-author

V ANHOUTTE P.M. Co-authors

SHIMOKA WA H.

Co-authors

67

Amplifying effect of serotonin in the control of vascular tone 69 Van Nueten J.M.

Amplification mechanisms in platelet activation 77 De Chaffoy de Courcelles D.

The role of the endothelium in the cardiovascular response to serotonin 81 Van Nueten J.M. and Janssens W.J.

Endothelium-dependent relaxations to serotonin: signal transduction and effects of diets 97 Flavahan N.A. and Vanhoutte P. M.

xiv

OWMANCH.

Co-authors

PLETSCHER A.

Co-authors

VAN DE KARL.D. Co-authors

VERBEUREN TJ.

HEISTAD D.D.

Co-authors

SYMOENSJ.

Co-author

- Central Nervons System:

CULLHEIMS. Co-authors

BARBACCIA M.L. Co-authors

RAITERIM. Co-authors

FUXEK.

Co-authors

WAUQUIERA.

Co-authors

GARATTINI S. Co-authors

LEIBOWITZ S.F.

Co-authors

BLUNDELL J.E.

Co-author

LEATHWOOD P.D.

5-Hydroxytryptamine in cerebrovascular sympathetic nerves and its effect on brain vessels Chang J.Y., Hardebo J.E. and Steinbusch H.W.M.

The 5-HT system of blood platelets: physiological variations and pathophysiology in essential hypertension Fetkovska N., Ferracin F., Arnstein R. and Buehler F.R.

Serotonergic regulation of renin and vasopressin secretion Urban J.H. and Brownfield M.S.

5HT, platelets and experimental atherosclerosis

Responses to serotonin in atherosclerotic and hypertensive blood vessels Lopez J.A.G. and Mayhan W.G.

Does the serotonin antagonist ketanserin have vascular protective effects? De ClerckF.

105

117

123

131

137

141

147

Serotonin and coexisting peptides in cat and lamprey spinal cord 149 Arvidsson U., Ultbake B., Hokfelt T., Christenson J., Brodin L., Wallen P. and Grillner S.

Is there an endogenous modulation of serotonin uptake? 155 WoodP.L. and Costa E.

Serotonin receptors regulating transmitter release 161 Maura G., Bonanno G., Pittaluga A., Fedele E., Costa C., Cerasoli M.G. and Ulivi M.

Galanin/5-HT receptor interactions. A new integrative mechanism in the control of 5-HT neurotransmission in the central nervous system 169 Agnati L.F., Von Euler G., Lundgren K., Zoli M., Bjelke B., Eneroth P. and Ogren S.O.

Changing views on the role of serotonergic mechanisms in the control of the sleep-wakefulness cycle 187 Dugovic C. and Janssen P.A.J.

Serotonin transmission and food intake 193 Caccia S., Mennini T. and Samanin R.

Serotonin in medial hypotholamic nuclei controls circadian patterns of macronutrient intake 203 Shor-Posner G. and Weiss G.F.

Serotonin receptor sub-types and the organisation of feeding behaviour: experimental models 213 LawtonC.L.

Tryptophan availability and serotonin synthesis 221

- Gastrointestinal System:

BECHK. Co-author

JAFFEB.M.

WOOD J.D.

SANGERG.J.

Co-author

Effects of serotonin on gastric secretion in vivo Johansen B.

Serotonin in intestinal function

Messenger function of Serotonin in the enteric nervous system

5-Hydroxytryptamine and cholinergic function in the gastrointestinal tract WardleK.A.

xv

227

229

235

241

251

SEROTONERGIC RECEPTORS: BIOCHEMISTRY, PHYSIOLOGY AND PHARMACOL-OGY 257

GLENNON R.A.

RICHARDSON B.P.

Co-author

AGHAJANIAN G.K.

Co-authors

WALKERR.J. Co-author

SLEIGHT A.J.

Co-author

GOTHERTM.

Co-author

MIDDLEMISS D.N. Co-authors

SANDERS-BUSH E. Co-author

NELSOND.L.

Co-author

LEYSENJ.E.

Co-author

FOZARDJ.R.

KILPATRICK G.J. Co-authors

Functional/clinical significance of 5-hydroxytryptamine binding sites

Selective agonists and antagonists at 5-hydroxytryptamine receptor subtypes HoyerD.

Electrophysiology of brain serotonin receptors: subtype specificity for

259

265

effector mechanisms 277 Sprouse I.S., Sheldon P. and Rasmussen K.

5-Hydroxytryptamine (5-RT) receptor subtypes in invertebrates 283 Vehovszky A.

5-HydroxytryptaminelA receptors: pharmacological and functional characterization 289 Peroutka SJ.

Modulation of serotonin release in the central nervous system via presynaptic S-HT autoreceptors 295 Schlicker E.

Receptor binding correlates of functional terminal 5-HT autoreceptors 301 Lee W.C., Smith S.M. and Tricklebank M.D.

Pharmacology, function and adaptive regulation of 5HT.1c receptors 309 TsutsumiM.

Classification of serotonergic receptors: an example of a noveI5-HT1-

like binding site in the rabbit caudate nucleus 317 XiongW.-C.

Central and peripheral 5-HTz receptors: role in physiological versus pathological conditions 323 Pauwels P.l.

5-HT3 receptors 331

Brain 5-HT3 receptors 339 Jones BJ. and Tyers M.B.

xvi

KAUMANN A.I. Co-authors

COHENM.L.

Co-authors

GERSHON M.D.

Co-authors

VOLTERRA A.

PALACIOS J.M.

Co-authors

Heart 5-IIT receptors. A novel5-IIT receptor in human atrium 347 Murray K.J., Brown A.M., Frampton J .E., Sanders L. and Brown M.J.

Characterization of the contractile 5IIT receptor in the rat stomach fundus 355 Secrest R.I. and Kauffman RF.

Peripheral neura15-IIT receptors: subtypes in the enteric nervous system 361 Wade P. and Branchek TA

Antagonistic modulation of A K+ channel activity by serotonin and the peptide FMRFamide in aplysia sensory neurons: molecular aspects and functional implications 373

Visualization of serotonin receptor binding and their messenger RNA's in the mammalian brain: an update 383 Waeber C., Mengod G. and Hoyer D.

PHARMACOLOGY OF SEROTONERGIC SYSTEM: 389

SICUTERIF.

Co-authors

SAXENAP.R.

ROBERTSON J.I.S.

SALVETTIA.

Co-authors

COFFMAN J.D. Co-authors

LEBRECD.

BEELEH.

Co-authors

LAPrERE CH. M.

ROOMANRP.

Co-authors

Upregulation of pain transmission from deficient serotonergic analgesia in migraine 391 Poggioni M. and Panconesi A.

Selective 5-hydroxytryptaminel-like receptor agonists and migraine 405

Recent insights into the antihypertensive mechanism of action of ketanserin 411

Ketanserin interactions with nifedipine and captopril: two italian cross over trials 417 Assogna G., Bossini A., Cagli V., Di Veroli C., Ladetto P. E., Lavez-zaro G.C., Stramignoni D., Valente M. and Zanna C.

International study ofketanserin in Raynaud's phenomenon 429 Dorrnandy J.A., Murray G.D. and Janssens M.

Serotonin and portal hypertension 435

Effects of serotonin and ketanserin on the functional morphology of skin: organotypical cultures of adult human skin and embryonic chick skin as experimental models 439 Thierens H. and De Ridder L.

Use of antagonists to 5-IIT2 receptors of serotonin by topical applica-tion in healing skin ulcers 447

Ketanserin in wound healing and fibrosis: investigations into its mechanism of action 451 Moeremans M., De Wever B., Daneels G., Geuens G., Aerts F. and De Brabander M.

- Central Nervous System

HYTTELJ.

BLOISR.

Co-authors

BRUNELLON.

Co-authors

RIVAM.

Co-author

BROWNS.L. Co-authors

COWENP.J. Co-author

DE MONTIGNY C.

Co-authors

DEAKIN J.F.W. Co-author

NAPPIG.

Co-authors

DE VRIJ J. Co-authors

MENDLEWICZ J. Co-authors

NIEMEGEERS, C.J.E. Co-authors

MARAZZITI D. Co-authors

- Neuroendocrine System

PREZIOSIP. Co-authors

HENINGER G.R.

Co-authors

xvii

457

Serotonin uptake inhibitors 459

Serotonergic re-uptake inhibition and depression: the effects of fluvoxamine on sleep in depressed patients 465 Bovier P., Gaillard J.M. and Tissot R.

Chronobiological studies of serotonin uptake complex: relevance to antidepressant action 471 Bianchi E., Racagni G. and Rovescalli A.C.

Lack of serotonergic influence on desipramine induced B-adrenergic receptor down-regulation 481 Creese I.

Serotonin in depression and anxiety 487 Kom M.L. and Van Praag H.M.

Investigations of 5-HT neuroendocrine function in depression 493 Anderson I.M.

Electrophysiological investigation of the effects of antidepressant treatments on serotonin receptors 499 Blier P. and Chaput Y.

Role of 5HT 2 receptors in anxiety and depression 505 WangM.

Effectiveness of ritanserin on pain and depression in chronic headache disorders 511 Sandrini G., Granella F., Ruiz L., Cerutti G., Micieli G. and Manzoni G.C.

5-HT1A receptor partial agonists as anxiolytics 517 Glaser T. and Traber J.

5HT2 receptor antagonism and slow wave sleep in man 523 Staner L., Kempenaers C., Simonnet M.P. and Fransolet L.

Serotonin involvement in the action of antipsychotic drugs 531 Awouters F. and Janssen P.A.J.

Serotonin control of anxiety 543 Perugi G. and Cassano G. B.

Endocrine changes and 5-hydroxytryptamine receptor subtypes Vacca M., Ragazzoni E. D' Amato M. and Navarra P.

Neuroendocrine effects of serotonin agonists in rhesus monkeys, healthy humans and patients with depression or anxiety disorders: effects of antidepressant treatment Charney D., Price L., Delgado P., Woods S. and Goodman W.

549

551

559

xviii

MURPHYD.L.

Co-authors

FALASClllP.

Co-authors

GUDELSKY G.A.

Co-authors

FULLERR.W.

Hormonal responses to serotonergic drugs as a means to evaluate brain serotonergic function in humans 565 Zohar J., Lawlor B.A., Sunderland T., Pigott T.A., Aulakh C.S., Bagdy G. and Garrick N.A.

Role of serotonin in the control of prolactin secretion: effect of antiserotoninergic drugs in normal subjects and in hyperprolactinaemic states 581 Rosa M., Rocco A., Proietti A., Pozzi F., Melis G.B.

Serotonin agonist induced corticosterone and prolactin secretion: role of 5-HTz and 5-HT1A receptors Nash J.F., Koenig J.I. and Meltzer H.Y.

Role of serotonin in regulation of the pituitary- adrenocortical axis in rats

589

SHORT AND LONG TERM EFFECTS OF SUBSTITUTED AMPHETAMINES

595

601

KLEVEN M.S.

Co-author

SCHAECHTER J.D.

Co-authors

LORENS S.A. Co-authors

APPELN.M.

Co-authors

ROWLAND N.E.

Co-authors

GARATTlNI S. Co-author

BLUNDELL J.E.

Co-author

BATTAGLIA G.

Index

Toxicity of amphetamine-related drugs and resulting behavioral changes SeidenL.S.

Effect of chronic D-fenfluramine administration on rat brain serotonin levels and release Laferrere B. and Wurtman R.J.

Behavioral effects of 5,7-DHT and MDMA treatment in rats Hata N., Cabrera T. and Hamilton M.E.

Immunohistochemical and autoradiographic investigations of high-dose

603

609

615

fenfluramine treatment on monoamine neurons in rat brain 625 Appel N.M., Zaczek R. Mitchell M. and De Souza E.

Long term actions of dexfenfluramine on food intake, body weight and brain serotonin in rodents 631 Souquet A.-M. and Edwards DJ.

Significance of fenfluramine neurotoxicity: a kinetic approach 637 Caccia S.

Effect of D-fenfluramine on appetite in lean and obese human subjects and on changes associated with PMS (pre-menstrual syndrome) 645 Hill A.J.

Criteria for assessing drug-induced biochemical alterations and degeneration of serotonergic neurons 651

661