Ciba Foundation Symposium 152 - The Biology of Nicotine Dependence

273 Pages·15.75 MB·English

THE BIOLOGY
OF NICOTINE
DEPENDENCE
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Limited. The Foundation operates independently in London under
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Ciba Foundation Symposium 152
________
THE BIOLOGY
OF NICOTINE
DEPENDENCE
A Wiley-lnterscience Publication
1990
JOHN WlLEY &. SONS
Chichester . New York . Brisbane . Toronto . Singapore
OCiba Foundation 1990
Published in 1990 by John Wiley & Sons Ltd.
Baffins Lane, Chichester
West Sussex PO19 IUD, England
All rights reserved.
No part of this book may be reproduced by any means,
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Suggested series entry for library catalogues:
Ciba Foundation Symposia
Ciba Foundation Symposium 152
264 pages, 41 figures, 19 tables
Library of Congress Cataloging-in-Publication Data
The Biology of nicotine dependence.
p. cm.-(Ciba Foundation symposium; 152)
Editors: Greg Bock and Joan Marsh.
Proceedings of a symposium held at the Ciba Foundation, London,
7-9 November 1989.
‘A Wiley-Interscience publication.’
Includes bibliographical references.
ISBN 0 471 92688 4
1. Nicotine-Physiological effect-Congresses. 2. Nicotinic
receptors-Congresses. 3. Tobacco habit-Physiological aspects-
Congresses. I. Bock, Gregory. 11. Marsh, Joan. 111. Series.
[ DNLM: 1. Nicotine-pharmacology-congresses. 2. Substance
Dependence-congresses. W3 C161F v. 152/QV 137 B615 19891
QP8Ol .N48B56 1990
616.865-dc20
DNLM/DLC
for Library of Congress 90-12213
CIP
British Library Cataloguing in Publication Data
The biology of nicotine dependence.
1. Man. Effects of nicotine
I. Bock, Greg 11. Marsh, Joan, 1960- 111. Series
615.78
ISBN 0 471 92688 4
Phototypeset by Dobbie Typesetting Limited, Devon.
Printed and bound in Great Britain by Biddles Ltd., Guildford.
Contents
Symposium on The biology of nicotine dependence held at the Ciba
Foundation, London 7-? Ncvember 1989
Editors: Greg Bock (Organizer) and Joan Marsh
L. L. Iversen Introduction’ 1
I. P. Stolerman Behavioural pharmacology of nicotine: implications for
multiple brain nicotinic receptors 3
Discussion 16
J. Lindstrom, R. Schoepfer, W. G. Conroy and P. Whiting Structural
and functional heterogeneity of nicotinic receptors 23
Discussion 43
J. H. Steinbach Mechanism of action of the nicotinic acetylcholine
receptor 53
Discussion 6 1
A. C. Collins, R. V. Bhat, J. R. Pauly and M. J. Marks Modulation of
nicotine receptors by chronic exposure to nicotinic agonists and
antagonists 68
Discussion 82
S. Wonnacott, A. Drasdo, E. Sanderson and P. Rowell Presynaptic
nicotinic receptors and the modulation of transmitter release 87
Discussion 102
General discussion I Inactivation of nicotinic cholinergic receptors 106
Location and function of nicotinic receptors in cultured cortical
neurons 109
K. Fuxe, L. F. Agnati, A. Jansson, G. von Euler, S. Tanganelli,
K. Anderson and P. Eneroth Regulation of endocrine function by the
nicotinic cholinergic receptor 1 13
Discussion 127
vi Contents
E. D. London Effects of nicotine on cerebral metabolism 131
Discussion 140
General discussion I1 Adaptive and cognitive aspects of the response to
nicotine 147
P. B. S. Clarke Mesolimbic dopamine activation-the key to nicotine
reinforcement? 153
Discussion 162
T. H. Svensson, J. Grenhoff and G. Engberg Effect of nicotine on
dynamic function of brain catecholamine neurons 169
Discussion 180
N. L. Benowitz Pharmacokinetic considerations in understanding nicotine
dependence 186
Discussion 200
R. J. West Nicotine pharmacodynamics: some unresolved issues 210
Discussion 2 19
0. F. Pomerleau and C. S. Pomerleau Behavioural studies in humans:
anxiety, stress and smoking 225
Discussion 235
Final discussion Withdrawal syndrome 240
Possible pharmacological therapies for nicotine 244
Use of transdermal nicotine patches to help people give up
smoking 250
Index of contributors 255
Subject index 251
Participants
M. Awad Department of Pharmacology, Faculty of Medicine,
Technion-Israel Institute of Technology, POB 9697, Haifa 3 1096, Israel
D. J. K. Balfour Department of Pharmacology & Clinical Pharmacology,
University of Dundee Medical School, Ninewells Hospital, Dundee
DDl 9SY, UK
N. L. Benowitz Division of Clinical Pharmacology & Experimental
Therapeutics, Building 30, 5th Floor, San Francisco General Hospital
Medical Center, 1001 Potero Avenue, San Francisco, California 941 10,
USA
J.-P. Changeux Unit of Molecular Neurobiology, Department of
Biotechnology, Institut Pasteur, 28 rue de Dr ROUXF, -75724 Paris,
cedex 15, France
P. B. S. Clarke Department of Pharmacology & Therapeutics, McGill
University, Suite 1325, McIntyre Medical Sciences Building, 3655
Drummond Street, Montreal, Quebec, Canada H3G 1Y6
A. C. Collins Institute for Behavioral Genetics, University of Colorado,
Campus Box 447, Boulder, Colorado 80309-0447, USA
D. Colquhoun Department of Pharmacology, University College London,
Gower Street, London WClE 6BT, UK
K. Fuxe Department of Histology, Karolinska Institute, Box 60400,
S-104 01 Stockholm 60, Sweden
J. A. Gray Department of Psychology, Institute of Psychiatry,
De Crespigny Park, Denmark Hill, London SE5 8AF, UK
N. E. Grunberg Department of Medical Psychology, Uniformed Services
University of the Health Sciences, 4301 Jones Bridge Road, Bethesda,
Maryland 20814-4799, USA
vti
viii Participants
S. Heinemann Molecular Neurobiology Laboratory, The Salk Institute,
PO Box 85800, San Diego, California 92138-9216, USA
J. E. Henningfield NIDA Addiction Research Center, PO BOX5 180,
Baltimore, Maryland 21224, USA
H. Howald K-125.12.20, CIBA-GEIGY Ltd, CH-4002 Basle, Switzerland
L. L. Iversen Neuroscience Research Centre, Merck, Sharp & Dohme
Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex
CM20 2QR, UK
K. J. Kellar Department of Pharmacology, Georgetown University
Medical Center, 3900 Reservoir Road, Washington DC 20007, USA
J. Lindstrom Receptor Biology Laboratory, The Salk Institute for
Biological Studies, PO Box 85800, San Diego, California 92138-9216,
USA
P. Lippiello RJ Reynolds Tobacco Co, Winston-Salem, North Carolina
27102, USA
E. D. London Neuropharmacology Laboratory, NIDA Addiction
Research Center, POB 5180, Baltimore, Maryland 21224, USA
G. G. Lunt Biochemistry Department, University of Bath, Claverton
Down, Bath BA2 7AY, UK
0. F. Pomerleau Department of Psychiatry, Behavioral Medical
Program, University of Michigan, Riverview Building, 900 Wall Street,
Ann Arbor, Michigan 48105, USA
J. E. Rose Nicotine Research Laboratory, VA Medical Center-Research
(151), 508 Fulton Street, Durham, North Carolina 27705, USA
M. A. H. Russell Health Behaviour Unit, Institute of Psychiatry,
De Crespigny Park, 101 Denmark Hill, London SE5 8AF, UK
R. D. Schwartz Department of Pharmacology, Box 3813, Duke
University Medical Center, Durham, North Carolina 277 10, USA
Participants ix
J. H. Steinbach Department of Anesthesiology, Washington University
School of Medicine, 660 South Euclid Avenue, St Louis, Missouri
63110, USA
I. P. Stolerrnan Department of Psychiatry, Institute of Psychiatry, De
Crespigny Park, 101 Denmark Hill, London SE5 8AF, UK
T. H. Svensson Department of Pharmacology, Karolinska Institute, Box
60400, S-104 01 Stockholm, Sweden
R. J. West Department of Psychology, Royal Holloway & Bedford New
College, Egham Hill, Egham, Surrey TW20 OEX, UK
S. Wonnacott Biochemistry Department, University of Bath, Claverton
Down, Bath BA2 7AY, UK
Novartis Foundation Symposium
Edited by Greg Bock, Joan Mash
Copyright 0 1990 by Ciba Foundation
Introduction
Leslie lversen
Neuroscience Research Centre, Merck, Sharp & Dohme Research Laboratories,
Terlings Park, Eastwick Road, Harlow, Essex CM20 ZQR, UK
The title of this symposium does not include the word ‘addiction’. Scientists
in general avoid the word because of the confusion between its popular and
scientific meanings. The term ‘drug dependence’ is more precise.
Drug dependence includes several different components. Usually, but not
always, continued administration of drugs of dependence leads to tolerance,
i.e. larger doses are needed to elicit the same effect after chronic usage. Physical
dependence is also a common but not invariable attribute of drugs of depen-
dence; physical dependence means that one can elicit a withdrawal syndrome
by removing the drug. In animal models, a more dramatic withdrawal syndrome
can sometimes be precipitated by the administration of an antagonist drug that
acts at the same receptor as the drug of dependence. In the case of opiates,
for example, there is a much better understanding of the withdrawal syndrome
in animal models since the advent of opiate antagonists such as naloxone and
naltrexone. In some cases it may be quite hard to see a consistent withdrawal
syndrome in animals unless an antagonist is used. It is only in the last few years
that reliable animal models have been available to study physical dependence
and withdrawal after chronic treatment with benzodiazepene tranquilizers. The
advent of such drugs as flumazenil (Ro 15-1788) as benzodiazapine receptor
antagonists proved to be very valuable in such studies. One of the research
tools we would like to have in studying each example of drug dependence is
antagonist drugs to probe the level of physical dependence that may develop.
A third facet of drug dependence is a very important one in leading to
compulsive drug abuse, namely the phenomenon of psychic craving-hard to
define scientifically and virtually impossible to understand in terms of brain
mechanisms.
This trio of factors describes the overall phenomenon of drug dependence
quite well. Some drugs may show only two of the three; some drugs may show
predominantly one feature and not the other two. Cannabis users, for example,
demonstrate psychic craving and abuse, but there is little evidence for physical
dependence or tolerance. Smokers develop some degree of tolerance and a clear
psychic craving for nicotine.
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