The Neuropharmacology of Nicotine Dependence (Current Topics in Behavioral Neurosciences Book 24)

The primary purpose of this book and its companion volume __The Behavioral Genetics of Nicotine and Tobacco__ is to explore the ways in which recent studies on nicotine and its role in tobacco addiction have opened our eyes to the psychopharmacological properties of this unique and fascinating drug. While __The Behavioral Genetics of Nicotine and Tobacco__ considers the molecular and genetic factors which influence behavioral responses to nicotine and how these may impact on the role of nicotine in tobacco dependence, the present book focuses on the complex neural and psychological mechanisms that mediate nicotine dependence in experimental animal models and their relationship to tobacco addiction in humans. These volumes will provide readers a contemporary overview of current research on nicotine psychopharmacology and its role in tobacco dependence from leaders in this field of researchand will hopefully prove valuable to those who are developing their own research programmes in this important topic. Preface 6 Contents 8 1 Imaging Tobacco Smoking with PET and SPECT 9 Abstract 9 1 Introduction 10 2 Imaging beta 2*-Nicotinic Acetylcholine Receptors 11 2.1 Preclinical Studies 11 2.2 Imaging the Upregulation of beta 2*-nAChRs in Tobacco Smokers 12 2.3 Imaging the Normalization of beta 2*-nAChRs in Tobacco Smokers 13 2.4 Sex Differences in beta 2*-nAChR Availability 14 2.5 Nicotine Occupancy of beta 2*-nAChRs 15 3 Imaging Dopamine Release in Response to Nicotine and Tobacco Smoking 16 3.1 Preclinical Microdialysis Studies 16 3.2 Imaging Dopamine Release with PET 17 3.3 Imaging Dopamine Release in Smokers 18 4 Imaging the Comorbidity of Tobacco Smoking with Schizophrenia 21 5 Conclusion 22 Acknowledgments 22 References 22 2 Behavioral Mechanisms Underlying Nicotine Reinforcement 26 Abstract 26 1 Introduction 27 2 Nicotine Self-administration 28 2.1 Outcome Measures 29 2.2 Route, Dose, and Rate of Nicotine 30 2.3 Food Restriction 32 2.4 Session Length 32 2.5 Sex and Age 33 2.6 Other Compounds in Cigarette Smoke 35 3 Primary Reinforcing Actions of Nicotine 38 4 Associative Learning and the Influence of Stimuli Predicting the Effects of Nicotine 39 4.1 Conditioned Responses to Nicotine-Associated Stimuli 39 4.2 Nicotine-Associated Stimuli as Conditioned Reinforcers 40 4.3 Nicotine-Associated Contexts as Discriminative Stimuli 41 4.4 Individual Differences in Associative Learning Effects 42 5 Associative Learning and the Influence of Nicotine as a Predictor of Other Reinforcers 43 6 Reinforcement-Enhancing Effects of Nicotine 43 6.1 Reinforcement-Enhancing Effects of Nicotine Occur Across Routes of Administration 44 6.2 Reinforcement-Enhancing Effects of Nicotine Occur Across Age and Sex 46 6.3 Reinforcement-Enhancing Effects of Nicotine Occur in Humans 47 6.4 Enhancement is Moderated by the Type and Nature of the Reinforcer 47 6.5 Implications of the Reinforcement-Enhancing Effect of Nicotine for Tobacco and Other Nicotine-containing Products 49 7 Summary and Conclusions 50 Acknowledgments 51 3 The Role of Mesoaccumbens Dopamine in Nicotine Dependence 61 Abstract 61 1 General Introduction 62 2 The Effects of Nicotine on DA Release from Mesolimbic DA Neurons In Vivo 63 3 Tonic and Phasic Firing of Mesolimbic Dopamine Neurons 67 3.1 The Effects of Nicotine on Phasic and Tonic Firing of Dopamine Neurons 70 4 The Role of Mesoaccumbens Dopamine Projections in Locomotor Responses to Nicotine 71 5 The Role of Mesolimbic Dopamine in Nicotine Dependence 73 5.1 Studies with Animal Models of Nicotine Reinforcement 73 5.2 Studies with Other Psychostimulant Drugs of Dependence 75 5.3 Does Extracellular Dopamine in the Accumbal Shell Have a Specific Role in Nicotine Dependence? 76 5.4 The Role of Hippocampal Projections in Dopamine Responses to Nicotine and Conditioned Contextual Stimuli 82 5.5 The Role of the Extracellular Dopamine in the Accumbal Core 83 6 Evidence for Tolerance to the Effects of Nicotine on Dopamine Release in the Nucleus Accumbens 84 7 The Implications for Our Understanding of the Psychobiology of Tobacco Dependence 87 7.1 The Role of Mesolimbic Dopamine in Pharmacotherapy for Tobacco Dependence 89 8 Conclusions 91 Acknowledgments 93 References 93 4 Nicotine Withdrawal 105 Abstract 105 1 Withdrawal Syndrome in Humans 106 1.1 Symptoms 106 1.2 Genetic Influences 106 2 Withdrawal Syndrome in Mice 109 2.1 Behavioral Manifestations and Testing Paradigms 109 3 Receptors and nAChR Subunits Underlying Withdrawal Symptoms 112 3.1 Insight from nAChR Subunit KO Mice 112 4 Molecular Mechanisms Involved in the Nicotine Withdrawal Syndrome 115 4.1 nAChR Upregulation 115 4.2 Desensitization of nAChRs 116 5 Anatomical Structures and Circuits Implicated in Nicotine Withdrawal 117 5.1 Dopaminergic System 117 5.2 Habenular Complex and Interpeduncular Nucleus 118 5.3 Hippocampus 119 5.4 Extended Amygdala 119 6 Summary and Research Moving Forward 120 Acknowledgments 121 References 121 5 Neurobiological Bases of Cue- and Nicotine-induced Reinstatement of Nicotine Seeking: Implications for the Development of Smoking Cessation Medications 130 Abstract 130 1 Introduction 131 2 Neurocircuits of Interest in Studies of the Reinstatement of Nicotine Seeking 133 2.1 Mesolimbic System 133 2.2 Habenulo-interpeduncular Circuit 134 2.3 Insular Cortex and Dorsal Striatum 135 3 Role of Various Neurotransmitter Systems in Cue- and Nicotine-induced Reinstatement of Nicotine-seeking Behavior 135 3.1 Acetylcholine 135 3.2 Glutamate 138 3.3 Dopamine 139 3.4 gamma -Aminobutyric Acid (GABA) 140 3.5 Endocannabinoids 140 3.6 Other Neurotransmitter Systems 142 4 Concluding Remarks 142 Acknowledgements 151 References 151 6 Psychiatric Disorders as Vulnerability Factors for Nicotine Addiction: What Have We Learned from Animal Models? 160 Abstract 160 1 Introduction 161 2 Addictive Disorder as Vulnerability for Nicotine Addiction 163 3 Schizophrenia as Vulnerability for Nicotine Addiction 164 3.1 The Dopamine Transporter Knockout Mouse 165 3.2 Neurodevelopmental Models of Schizophrenia 165 3.3 The Pre-pulse Inhibition Model of Schizophrenia 165 4 Mood Disorders as Vulnerability for Nicotine Addiction 166 4.1 Nicotine Effects in Untreated Rodents 166 4.2 Nicotine Effects in Rat Strains that Model Depression 167 4.3 Nicotine Effects in Environmentally Induced Models of Depression 167 5 Anxiety Disorders as Vulnerability for Nicotine Addiction 168 5.1 Acute Systemic Nicotine and Anxiety 168 5.2 Chronic Nicotine and Anxiety 169 5.3 Nicotine in Development and Anxiety 170 6 Conclusions 170 Acknowledgments 171 References 171 Index 176 The primary purpose of this book and its companion volume The Behavioral Genetics of Nicotine and Tobacco is to explore the ways in which recent studies on nicotine and its role in tobacco addiction have opened our eyes to the psychopharmacological properties of this unique and fascinating drug. While The Behavioral Genetics of Nicotine and Tobacco considers the molecular and genetic factors which influence behavioral responses to nicotine and how these may impact on the role of nicotine in tobacco dependence, the present book focuses on the complex neural and psychological mechanisms that mediate nicotine dependence in experimental animal models and their relationship to tobacco addiction in humans.℗l These volumes will provide readers a contemporary overview of current research on nicotine psychopharmacology and its role in tobacco dependence from leaders in this field of researchand will hopefully prove valuable to those who are developing their own research programmes in this important topic Front Matter....Pages i-vii Imaging Tobacco Smoking with PET and SPECT....Pages 1-17 Behavioral Mechanisms Underlying Nicotine Reinforcement....Pages 19-53 The Role of Mesoaccumbens Dopamine in Nicotine Dependence....Pages 55-98 Nicotine Withdrawal....Pages 99-123 Neurobiological Bases of Cue- and Nicotine-induced Reinstatement of Nicotine Seeking: Implications for the Development of Smoking Cessation Medications....Pages 125-154 Psychiatric Disorders as Vulnerability Factors for Nicotine Addiction: What Have We Learned from Animal Models?....Pages 155-170 Back Matter....Pages 171-172