1;Preface;5 1.1;References;7 2;Contents;9 3;Contributors;11 4;Nicotine and Tobacco Consumption: Measurement and Trends;15 4.1;Global Patterns of Nicotine and Tobacco Consumption;16 4.1.1;1 A History of Tobacco;17 4.1.2;2 Tobacco Today;19 4.1.3;3 Types of Tobacco Products;34 4.1.4;4 Tobacco Use by Gender and Age;36 4.1.5;5 Tobacco Use in the USA;37 4.1.6;6 Conclusion;39 4.1.7;References;39 4.2;Nicotine Chemistry, Metabolism, Kinetics and Biomarkers;42 4.2.1;1 Introduction;43 4.2.2;2 Nicotine and Related Alkaloids in Tobacco Products;43 4.2.3;3 Absorption of Nicotine;44 4.2.4;4 Distribution of Nicotine in Body Tissues;47 4.2.5;5 Metabolism of Nicotine;48 4.2.6;6 Factors Influencing Nicotine Metabolism;53 4.2.7;7 Renal Excretion;60 4.2.8;8 Nicotine and Cotinine Blood Levels During Tobacco Use and Nicotine Replacement Therapy;61 4.2.9;9 Biomarkers of Nicotine Exposure;62 4.2.10;References;67 4.3;Nicotine Content and Delivery Across Tobacco Products;74 4.3.1;1 Introduction;75 4.3.2;2 Nicotine Content in Cured Tobacco Leaves;76 4.3.3;3 Nicotine Content in Factory-Made Cigarettes;78 4.3.4;4 Nicotine Content in Other Combustible Tobacco Products;84 4.3.5;5 Nicotine in Smokeless Tobacco Products;89 4.3.6;6 Summary;91 4.3.7;References;91 5;Nicotine Pharmacology and Mechanisms of Action;96 5.1;The Road to Discovery of Neuronal Nicotinic Cholinergic Receptor Subtypes;97 5.1.1;1 Introduction;98 5.1.2;2 Receptive Substance, the Beginnings of a Field of Study;99 5.1.3;3 Pharmacological Approaches Identify Receptor Subtypes;100 5.1.4;4 Identification of a7* nAChRs;102 5.1.5;5 Heteromeric Receptors Containing a4 and ß2 Subunits: a4ß2*;106 5.1.6;6 Receptor Subtypes Expressed in Dopamine Neurons;112 5.1.7;7 Summary and Conclusions;116 5.1.8;References;117 5.2;Magnetic Resonance Imaging Studies of Cigarette Smoking;125 5.2.1;1 Introduction;126 5.2.2;2 Studies of Brain Structure;126 5.2.3;3 Proton Magnetic Resonance Spectroscopy (1HMRS);130 5.2.4;4 Functional Magnetic Resonance Imaging;136 5.2.5;5 Neural Responses to Stimuli Associated with Smoking;136 5.2.6;6 Cognitive Effects Related to Smoking;142 5.2.7;7 Sustained Attention andWorking Memory;144 5.2.8;8 Effects of Nicotine in Nonsmokers;146 5.2.9;References;150 5.3;In vivo Brain Imaging of Human Exposure to Nicotine and Tobacco;156 5.3.1;1 Introduction;157 5.3.2;2 Brain Function Responses to Acute Nicotine Administration and Cigarette Smoking;158 5.3.3;3 Brain Function Responses to Chronic Nicotine Administration and Cigarette Smoking;167 5.3.4;4 Discussion: Functional Neuroanatomy of Tobacco Use and Dependence;170 5.3.5;5 Future Directions;173 5.3.6;References;173 5.4;Molecular and Cellular Mechanisms of Action of Nicotine in the CNS;183 5.4.1;1 Introduction;184 5.4.2;2 Acute Effects of Nicotine on nAChRs;184 5.4.3;3 Effects of Chronic Nicotine;197 5.4.4;4 Concluding Remarks;206 5.4.5;References;207 5.5;The Neuronal Pathways Mediating the Behavioral and Addictive Properties of Nicotine;218 5.5.1;1 Introduction;219 5.5.2;2 The Role of Mesolimbic Dopamine;220 5.5.3;3 The Role of the Dorsal Striatum;229 5.5.4;4 The Neurobiology Underlying Nicotine Withdrawal;230 5.5.5;5 The Putative Role of Serotonergic Pathways in Nicotine Dependence;231 5.5.6;6 The Role of Metabotropic Glutamatergic Receptors in Behavioural Measures of Nicotine Dependence;233 5.5.7;7 The Role of Cannabinoid Receptors;234 5.5.8;8 Conclusions;237 5.5.9;References;238 5.6;Molecular Genetics of Nicotine Metabolism;243 5.6.1;Abbreviations;244 5.6.2;1 Introduction;244 5.6.3;2 Humans;245 5.6.4;3 Nonhuman Primate Nicotine Metabolism;256 5.6.5;4 Mouse Nicotine Metabolism;257 5.6.6;5 Rat Nicotine Metabolism;258 5.6.7;6 Conclusions;259 5.6.8;References;259 5.7;Sex Differences in Nicotine Action;268 5.7.1;1 Introduction;269 5.7.2;2 Nicotine Metabolism;271 5.7.3;3 Locomotor Activity;273 5.7.4;4 Reward Systems;275 5.7.5;5 Genetics;277 5.7.6;6 Development: Prenatal and Adolescent Exposure;278 5.7.7;7 Nicotinic Receptors;280 5.7.8;8 Consummat