The Motivational Impact of Nicotine and its Role in Tobacco Use (eBook)

Preface 6
Contributors 7
Contents 10
to 1 Nicotine, Tobacco Use, and the 55th Nebraska Symposium on Motivation 12
to 2 Synaptic Plasticity Within Midbrain Dopamine Centers Contributes to Nicotine Addiction 15
Introduction to the Health Problem 15
Midbrain Dopaminergic Systems 16
Action of Nicotine at Nicotinic Receptors in the Midbrain 17
Nicotine Influences Over Midbrain Synaptic Function 19
to 3 Molecular Mechanisms Underlying the Motivational Effects of Nicotine 26
Introduction 26
Cues and Nicotine Dependence 26
Prior Chronic Nicotine Exposure Enhances Conditioned Reinforcement 27
Desensitization of nAChRs May Underlie the Ability of Nicotine to Enhance Cue Salience 28
Brain Areas Important for Nicotine's Effects on Cue Responding 29
Role of DA in Nicotine-Mediated Behaviors 30
nAChR Subtypes Involved in Modulating the DA System 31
Intracellular Signaling Downstream of nAChRs 32
Conclusions 33
to 4 Targeting Reward-Relevant Nicotinic Receptors in the Discovery of Novel Pharmacotherapeutic Agents to Treat Tobacco Dependence 40
Introduction 40
Tobacco Alkaloids and Tobacco Use 40
Nicotinic Receptor-Mediated Dopamine Release in Nicotine Reward 40
Nicotinic Receptor Subtypes 42
nAChR Antagonists 44
Approved Smoking Cessation Pharmacotherapies 44
Novel nAChR Antagonists 45
Methods 47
Animals 47
Synthesis of Analogs 47
[ 3 H]DA Release Assay 48
Nicotine-Induced Reinstatement of Nicotine Self-Administration 49
Results and Discussion 50
[ 3 H]DA Release Assay 50
Nicotine-Induced Reinstatement of Nicotine Self-Administration 58
to 5 Multiple Motivational Forces Contribute to Nicotine Dependence 73
Introduction 73
Rewarding Effects of Nicotine 74
Primary Rewarding Effects of Nicotine 74
Conditioned Rewarding Effects of Stimuli Associated with Nicotine Administration 76
Reward-Enhancing Effects of Nicotine 78
Primary Reward-Enhancing Effects of Nicotine 78
Conditioned Reward-Enhancing Effects of Psychomotor Stimulants 79
Nicotine Withdrawal 81
Decreased Brain Reward Function during Nicotine Withdrawal 81
The Somatic Aspects of Nicotine Withdrawal 83
Motivational Significance of Anhedonic Versus Somatic Components of Drug Withdrawal 83
Conditioned Nicotine Withdrawal 85
Cognitive-Enhancing Effects of Nicotine 90
Conclusions 91
to 6 The Role of Nicotine in Smoking: A Dual-Reinforcement Model 98
Introduction 98
Role of Non-Nicotine Stimuli in Self-Administration and Smoking 99
Dual Reinforcing Effects of Nicotine 102
Predictions of the Dual-Reinforcement Model: Reinforcing Strength of the Nonpharmacological Stimulus 103
Predictions of the Dual-Reinforcement Model: Behavioral Dissociation 104
Predictions of the Dual-Reinforcement Model: Pharmacological Dissociation 107
Predictions of the Dual-Reinforcement Model: Role of Conditioning 108
Nature and Temporal Dynamics of Nicotine's Reinforcement-Enhancing Effects 110
Significance of the Dual-Reinforcement Model 111
Summary and Conclusions 112
to 7 Altering the Motivational Function of Nicotine through Conditioning Processes 117
Introduction 117
Nicotine as a Reinforcer 118
Nicotine as a Discriminative Stimulus 121
Interoceptive Pavlovian Conditioning: A Historical Framework 123
Nicotine as an Interoceptive CS 124
Nicotine as an Interoceptive Occasion Setter 128
Implications for the Motivational Function of Nicotine 130
to 8 New Findings on Nicotine Addiction and Treatment 136
Introduction 136
Pre-cessation Administration of Pharmacologic Agents 136
Pre-cessation use of Nicotine Replacement Therapy 136
Varenicline 140
Pre-cessation Mecamylamine Treatment 141
Pre-cessation Bupropion Treatment 141
Nicotine Vaccine 141
Tailoring Smoking Cessation Treatment Based on Genetics 143
Conclusion 143
Financial Disclosure 144
to 9 Sex Differences in Nicotine Reinforcement and Reward: Influences on the Persistence of Tobacco Smoking 147
Introduction 147
Clinical Implications of Sex Differences in Factors Promoting Smoking Persistence 148
Possible Sources of Sex Differences in Smoking Reinforcement 149
Pharmacokinetic 149
Pharmacodynamic 150
Non-pharmacological 150
Gender 151
Reduced Sensitivity to Nicotine Reinforcement and Reward in Women Versus Men 151
Direct Effects of Nicotine on Self-administration Behavior and Reward Ratings 152
Ad Lib Self-administration of Nicotine Nasal Spray 152
Nicotine Versus Placebo Spray Choice 153
Reinforcing and Rewarding Effects of Nicotine Dose via Cigarettes 154
Influence of Nicotine Pre-treatment on Subsequent Nicotine or Smoking Reinforcement 154
Ad lib Smoking Following Nicotine Spray Pre-treatment 156
Nicotines Spray Choice Following Nicotine Patch Pre-treatment 156
Other Relevant Findings 157
Sex Differences in Non-Pharmacological Influences of Smoking 157
Sex Differences in Sensitivity to Nonverbal Drug Information (Cues) 158
Smoking Reinforcement due to Lit Cigarette Cue 158
Smoking Reward and Reinforcement after Blocking Smoking Cues 159
Sex Differences in Sensitivity to Verbal Drug Information (Expectancies) 159
Sex Differences in the Reinforcing Effects of Control over Smoking 162
Other Relevant Findings 164
Clinical Implications 165
Sex Differences in NRT Efficacy 165
Sex Differences in Response to Other Medications 167
Sex Differences in Treatments Aimed at Non-Nicotine Influences on Smoking 167
Conclusions and Future Directions 168
to 10 The Functional Significance of Craving in Nicotine Dependence 174
Introduction 174
Conventional Craving Assumptions 175
How Do We Study Craving? 176
Craving Assessment 176
Factors that Affect Cigarette Craving 177
Cigarette Abstinence 177
Time of Day 178
Alcohol Intoxication 179
Stress and Negative Affect 179
Smoking-Related Cues 179
Cigarette Availability and Craving 181
Tonic -- Phasic Distinction in Cigarette Craving 183
Craving and Drug Use 183
Addressing the Craving-- Drug Use Conundrum 184
If Craving and Smoking Are Not Tightly Coupled, Why Study Craving? 188
Ubiquity of Craving Among Smokers 188
Prominence of Craving Among Abstinent Smokers 188
Aversive Nature of Craving 189
Craving as a Predictor of Relapse 190
Craving as a Core Attribute of Nicotine Dependence 190
Future of Craving Research 192
Final Note 194
to 11 The Motivational Impact of Nicotine and Its Role in Tobacco Use: Final Comments and Priorities 201
Some Final Comments 201
Future Priorities: The NIH Perspective 203
Long-Term Surveys of Tobacco Use 203
Genetics/Epigenetics 204
Nicotine Vaccine 204
Drug Exposure and Development 204
Co-morbidity 205
Neurobiological Substrates of Behavior 205
National Cooperative Drug Discovery Group (NCDDG) 205
Index 1