Table Of ContentNEUROSCIENCE
lNTELLI GENCE
UNIT
CHOLECYSTOKININ
AND ANXIETY:
FROM NEURON TO BEHAVIOR
Jacques Bradwejn, M.D., ER C.P.C.
University ofToronto
Toronto, Ontario, Canada
Eero Vasar, M.D., Ph.D.
University ofTartu
Tartu, Estonia
Springer-Verlag Berlin Heidelberg GmbH
RG.lANDES COMPANY
AusTIN
NEUROSCIENCE INTELLIGENCE UNIT
CHOLECYSTOKININ AND ANXIETY: FROM NEURON TO BEHAVIOR
R.G. LANDES COMPANY
Austin, Texas, U.S.A.
Submitted: June 1995
Published: August 1995
U.S. and Canada Copyright © 1995 R.G. Landes Company
All rights reserved.
U.S. and Canada ISBN 978-3-662-21707-8
International Copyright © 1995 Springer-Verlag Berlin Heidelberg
Originally published by Springer-Verlag, Heidelberg Germany 1995
Softcover reprint of the hardcover 1st edition 1995
All rights reserved.
International ISBN 978-3-662-21707-8
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Library of Congress Cataloging-in-Publication Data
Cholecystokinin and anxiety: from neuron to behavior I [edited by}
Jacques Bradwejn, Eero Vasar.
p. em. - (Neuroscience intelligence unit)
Includes bibliographical references and index.
ISBN 978-3-662-21707-8 ISBN 978-3-662-21705-4 (eBook)
DOI 10.1007/978-3-662-21705-4
1. Anxiety-Pathophysiology. 2. Cholecystokinin-Psychotropic effect.
I. Bradwejn, Jacques, 1952- . II. Vasae, Eero. III. Series.
[DNLM: 1. Anxiety-physiopathology. 2. Choelecystokinin-physiology. WM172
C547 1995]
RC53l.C46 1995
616.85'22307-dc20
DNLM/DLC 95-548
for Library of Congress CIP
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r.======= CONTENTS======;-]
1. Neurobiology of Anxiety and Panic ............................................ 1
Nick J Coupland and David J Nutt
What Should Neurobiological Theories
of Anxiety and Panic Explain? ............................................................ 1
Role of Challenge Tests .................................................... : .................... 2
A Role for Abnormal Respiratory Physiology? ....................................... 4
Noradrenergic System ........................................................................... 6
Benzodiazepine Receptor System ........................................................ 10
Serotonergic System ............................................................................ 14
Other Panico gens ................................................................................ 15
Cognitive Considerations .................................................................... 15
The Future .......................................................................................... 24
2. Molecular Forms and Regional Distribution
of Cholecystokinin in the Central Nervous System ................... 33
fens F. Rehfeld and Finn Cilius Nielsen
Introduction ....................................................................................... 33
History of CCK .................................................................................. 34
Biogenesis of CCK Peptides in Neurons ............................................. 36
Molecular Forms of CCK in the Brain ................................................ 38
Regional Distribution of CCK in the Brain ........................................ 41
Extracerebral Expression ofProCCK ................................................... 43
CCK Peptides as Neurotransmitters .................................................... 43
Problems in the Identification of Neuronal CCK Peptides .................. 45
Molecular Forms of Gastrin in the Brain ............................................. 48
Conclusion .......................................................................................... 49
3. Animal Studies on CCK and Anxiety ........................................ 57
jaanus Harro, Eero Vasar, Lars Oreland and Pekka T. Miinnisto
Anxiety-Related Behavioral Phenomena
with CCK Receptor Ligands ............................................................ 57
Site of the Anxiogenic Action of CCK in Rodents ............................... 61
Changes in the CCKergic Mechanisms in Anxiety States .................... 62
Animal Studies on Anxiety-Related Neurotransmitter Interactions ..... 64
4. Cholecystokinin and Panic Disorder ......................................... 73
jacques Bradwejn
CCK Hypothesis of Panic Disorder: Historical Perspective ................. 73
Validation of CCK-4 as a Panicogenic Agent ...................................... 74
Comparison of the Effects ofCCK-4 to Those Produced by C0 78
2 .......
Mechanism of Anxiogenic Action of CCK-4 ....................................... 79
Conclusion .......................................................................................... 82
5. Psychological Factors and Response to Cholecystokinin ........... 87
Diana Koszycki
Introduction ....................................................................................... 87
Cognitive Attribution ......................................................................... 88
Anxiety Sensitivity .............................................................................. 91
Personality Correlates .......................................................................... 93
Baseline Anxiety .................................................................................. 95
Summary ............................................................................................ 96
6. Interactions Between Cholecystokinin
and Other Neurotransmitter Systems ..................................... 101
jacqueline N. Crawley
Introduction ..................................................................................... 101
Central Nervous System .................................................................... 102
Periphery .......................................................................................... 109
Issues Outstanding ............................................................................ 113
Conclusion ........................................................................................ 115
7. CCK, Addiction and Anxiety .................................................. 127
Franco Vaccarino
Drug Dependence and Withdrawal:
Role of CCK Anxiogenic Processes ................................................ 127
Drug Withdrawal .............................................................................. 128
Drug Withdrawal and Anxiety .......................................................... 129
CCK, Drug Withdrawal and Anxiety ................................................ 130
CCK-Dopamine Interactions: Relevance to Reward Processes .......... 132
Drug Reward and Dopamine ............................................................ 133
Food Reward and Dopamine ............................................................ 133
Individual Differences in Responsiveness
to Psychostimulant Drugs .............................................................. 134
Relation Between Reward, Locomotion and Feeding ........................ 136
CCK-Dopamine Interactions in Reward-Relevant Behaviors ............ 137
Psychostimulants and Locomotor Activation .................................... 137
Brain Stimulation and Drug Reward ................................................. 139
Individual Differences in Responsiveness to Amphetamine ............... 140
Proposed Mechanisms for CCK-Dopamine Interactions
in Drug Reward ............................................................................. 141
Possible Relevance of CCK Reward Effects
to Anxiety Mechanisms .................................................................. 142
8. Opioid and CCK Systems in Anxiety and Reward .................. 151
Valerie Dauge and Bernard P. Roques
Introduction ..................................................................................... 151
Design of CCK-8-Derived Peptidomimetics Selective
for CCK-B Receptor ...................................................................... 154
Evidence for the Involvement of CCK
in "Anxiety"/Fear in Rodents and Monkeys ................................... 155
Anatomical Substrate ofCCK-InducingAnxiogenic-Like Effects ...... 159
Evidence of Antidepressant-Like Effects Induced by CCK-B
Antagonists: Interaction with the Enkephalinergic System ............. 162
Conclusion ........................................................................................ 164
9. Summary and Future Directions ............................................. 173
jacques Bradwejn and Eero Vasar
Summary .......................................................................................... 173
Future Directions .............................................................................. 176
Index .............................................................................................. 183
rr========EDITORS========,-J
Jacques Bradwejn, M.D., F.R.C.P.C.
Professor of Psychiatry
Head, Psychobiology and Clinical Trials Research Unit in Anxiety
The Clarke Institute of Psychiatry
University ofToronto
Toronto, Ontario, Canada
Chapters 4, 9
Eero Vasar, M.D., Ph.D.
Professor and Head,
Insitute of Physiology
University ofTartu
T artu, Estonia
Chapters 3, 9
CONTRIBUTORS
I===== =====I
Nick}. Coupland, D.M., Valerie Dauge, Ph.D.
M.R.C.P., M.R.C. Psych Universite Rene Descartes (Paris V)
Psychopharmacology Unit Departement de Pharmacochimie
School of Medical Sciences Moleculaire et Structurale
Bristol, Avon, United Kingdom Paris, France
Chapter I ChapterS
Jacqueline N. Crawley, Ph.D. Jaanus Harro, M.D., Ph.D.
Chief, Section on Behavioral Department of Pharmacology
Neuropharmacology, University ofTartu
Experimental Therapeutics T artu, Estonia
Branch Chapter3
National Institutes of Health
Bethesda, Maryland, U.S.A. Diana Koszycki, Ph.D.
Chapter6 Psychobiology and Clinical Trials
Research Unit in Anxiety
The Clarke Institute of Psychiatry
Toronto, Ontario, Canada
Chapter 5
