Understanding Nicotine and Tobacco Addiction

Symposium on Understanding nicotine and tobacco addiction, held at the Novartis Foundation, London, 17–19 May 2005

Editors: Gregory Bock (Organizer) and Jamie Goode

This symposium is based on a proposal made by Robert West and Gino van Heeke

William A. Corrigall Chair’s introduction 1

Richard Peto and Richard Doll The hazards of smoking and the benefits of stopping 3

Discussion 15

Ian Stolerman Animal models for nicotine dependence 17

Discussion 28

Robert West Defining and assessing nicotine dependence in humans 36

Discussion 52

General discussion I 59

Uwe Maskos, Sylvie Granon, Philippe Faure and Jean-Pierre Changeux Nicotinic acetylcholine receptor functions in the CNS investigated with a novel method of stereotaxic gene re-expression in knockout mice 64

Discussion 79

Marina R. Picciotto Nicotine-mediated activation of signal transduction pathways 83

Discussion 90

David Balfour Complementary roles for the accumbal shell and core in nicotine dependence 96

Discussion 105

Christian Heidbreder The dopamine D3 system: new opportunities for dopamine-based reward 116

Discussion 123

Athina Markou Pathways and systems involved in nicotine dependence 132

Discussion 145

Arthur L. Brody Localizing tobacco dependence pathways with functional brain imaging 153

Discussion 166

Caryn Lerman Pharmacogenetic approach to nicotine dependence treatment 171

Discussion 178

Robert Walton Pharmacogenomics and smoking cessation 184

Discussion 194

General discussion II Power in studies 197

Receptor desensitization 199

Peter Hajek What limits the efficacy of current nicotine replacement therapies? 204

Discussion 213

Saul Shiffman, Stuart Ferguson and Deborah Scharf Exploring behavioural mechanisms of nicotine replacement therapy for smoking cessation 219

Discussion 231

Rachel F. Tyndale and Edward M. Sellers Modifying the metabolism of nicotine as a therapeutic strategy 235

Discussion 244

William A. Corrigall Challenges in discovery and development of pharmacotherapies for tobacco addiction 249

Discussion 259

Final discussion Nicotine comorbidity 262

Animal models 264

Index of contributors 266

Subject index 268