Nicotine Psychopharmacology (eBook)

Preface 5
References 7
Contents 9
Contributors 11
Nicotine and Tobacco Consumption: Measurement and Trends 15
Global Patterns of Nicotine and Tobacco Consumption 16
1 A History of Tobacco 17
2 Tobacco Today 19
3 Types of Tobacco Products 34
4 Tobacco Use by Gender and Age 36
5 Tobacco Use in the USA 37
6 Conclusion 39
References 39
Nicotine Chemistry, Metabolism, Kinetics and Biomarkers 42
1 Introduction 43
2 Nicotine and Related Alkaloids in Tobacco Products 43
3 Absorption of Nicotine 44
4 Distribution of Nicotine in Body Tissues 47
5 Metabolism of Nicotine 48
6 Factors Influencing Nicotine Metabolism 53
7 Renal Excretion 60
8 Nicotine and Cotinine Blood Levels During Tobacco Use and Nicotine Replacement Therapy 61
9 Biomarkers of Nicotine Exposure 62
References 67
Nicotine Content and Delivery Across Tobacco Products 74
1 Introduction 75
2 Nicotine Content in Cured Tobacco Leaves 76
3 Nicotine Content in Factory-Made Cigarettes 78
4 Nicotine Content in Other Combustible Tobacco Products 84
5 Nicotine in Smokeless Tobacco Products 89
6 Summary 91
References 91
Nicotine Pharmacology and Mechanisms of Action 96
The Road to Discovery of Neuronal Nicotinic Cholinergic Receptor Subtypes 97
1 Introduction 98
2 Receptive Substance, the Beginnings of a Field of Study 99
3 Pharmacological Approaches Identify Receptor Subtypes 100
4 Identification of a7* nAChRs 102
5 Heteromeric Receptors Containing a4 and ß2 Subunits: a4ß2* 106
6 Receptor Subtypes Expressed in Dopamine Neurons 112
7 Summary and Conclusions 116
References 117
Magnetic Resonance Imaging Studies of Cigarette Smoking 125
1 Introduction 126
2 Studies of Brain Structure 126
3 Proton Magnetic Resonance Spectroscopy (1HMRS) 130
4 Functional Magnetic Resonance Imaging 136
5 Neural Responses to Stimuli Associated with Smoking 136
6 Cognitive Effects Related to Smoking 142
7 Sustained Attention andWorking Memory 144
8 Effects of Nicotine in Nonsmokers 146
References 150
In vivo Brain Imaging of Human Exposure to Nicotine and Tobacco 156
1 Introduction 157
2 Brain Function Responses to Acute Nicotine Administration and Cigarette Smoking 158
3 Brain Function Responses to Chronic Nicotine Administration and Cigarette Smoking 167
4 Discussion: Functional Neuroanatomy of Tobacco Use and Dependence 170
5 Future Directions 173
References 173
Molecular and Cellular Mechanisms of Action of Nicotine in the CNS 183
1 Introduction 184
2 Acute Effects of Nicotine on nAChRs 184
3 Effects of Chronic Nicotine 197
4 Concluding Remarks 206
References 207
The Neuronal Pathways Mediating the Behavioral and Addictive Properties of Nicotine 218
1 Introduction 219
2 The Role of Mesolimbic Dopamine 220
3 The Role of the Dorsal Striatum 229
4 The Neurobiology Underlying Nicotine Withdrawal 230
5 The Putative Role of Serotonergic Pathways in Nicotine Dependence 231
6 The Role of Metabotropic Glutamatergic Receptors in Behavioural Measures of Nicotine Dependence 233
7 The Role of Cannabinoid Receptors 234
8 Conclusions 237
References 238
Molecular Genetics of Nicotine Metabolism 243
Abbreviations 244
1 Introduction 244
2 Humans 245
3 Nonhuman Primate Nicotine Metabolism 256
4 Mouse Nicotine Metabolism 257
5 Rat Nicotine Metabolism 258
6 Conclusions 259
References 259
Sex Differences in Nicotine Action 268
1 Introduction 269
2 Nicotine Metabolism 271
3 Locomotor Activity 273
4 Reward Systems 275
5 Genetics 277
6 Development: Prenatal and Adolescent Exposure 278
7 Nicotinic Receptors 280
8 Consummatory Behavior and BodyWeight 281
9 Self-Administration 283
10 Cognitive Effects 285
11 HPA Axis, Anxiety, and Stress 287
12 Neuropsychiatric Disorders 289
13 Smoking Cessation 289
14 Concluding Remarks 290
References 290
Nicotine Psychopharmacology 299
Recognising Nicotine: The Neurobiological Basis of Nicotine Discrimination 300
Abbreviations 301
1 Introduction 302
2 The Basis of Drug Discrimination 304
3 Factors that Modulate Nicotine Discrimination 305
4 Neuroanatomical Origin of Nicotine Discriminations 312
5 Primary Pharmacological Origins 313
6 Secondary Pharmacological Mediation 320
7 Conclusions 327
References 330
Effects of Nicotine in Experimental Animals and Humans: An Update on Addictive Properties 339
1 Introduction 340
2 Experimental Procedures for Studying NicotineÌs Effects 341
3 Effects of Nicotine in Experimental Animals and Humans 344
4 Conclusions 360
References 361
Discriminative Stimulus Effects of Nicotine in Humans 372
1 Introduction 373
2 Characterizing Nicotine Discrimination 376
3 Moderators of Nicotine Discrimination 383
4 Conclusions 397
References 399
Rodent Models of Nicotine Withdrawal Syndrome 404
1 Introduction 405
2 Types of Rodent Models 407
3 Issues of Validity 414
4 Anatomical Correlates 416
5 Neurochemical Correlates 421
6 Developmental Factors 427
7 Evaluating Potential Therapies 428
8 Directions for Future Research 429
References 430
Nicotine and Tobacco Product Regulation 438
Approaches, Challenges, and Experience in Assessing Free Nicotine 439
1 Introduction 440
2 Tobacco Industry Findings 443
3 Free Nicotine in Tobacco Smoke 449
4 Free Nicotine in Smokeless Tobacco 453
5 Summary 456
References 456
Tobacco Industry Manipulation of Nicotine Dosing 459
1 Introduction 460
2 Factors in Nicotine Dosing 462
3 Methods for Manipulating Nicotine Dosing 470
4 Implications for the Commercial Market 475
5 Conclusions 478
References 480
Pharmacotherapy for Tobacco Dependence 488
Financial Disclosures 489
1 Introduction 489
2 Nicotine Replacement 491
3 Nicotine Partial Agonists 498
4 Nicotine Antagonists 498
5 Nicotine Vaccines 499
6 Drugs Modulating Monoamine Neurotransmitters 501
7 Dopamine D3 Receptor Antagonists 502
8 a2-Noradrenergic Agonists 503
9 Cannabinoid Antagonists 503
10 Discussion 504
References 505
Nicotine Psychopharmacology: Policy and Regulatory 512
1 The Dawn of Neuropharmacology and the Science of Drug Addiction 514
2 1964 Surgeon GeneralÌs Report on Smoking and Health 515
3 Explosion of Nicotine Psychopharmacology Research in the 1970s 516
4 Scientific Questions Concerning Nicotine as an Addictive Drug 518
5 1980s Research Strengthened the Foundation for the 1988 Surgeon GeneralÌs Report and FDA Regulation of Tobacco 519
6 Nicotine Psychopharmacology Research was Pivotal in FDA's Conclusions that Cigarettes and Smokeless Tobacco are Addicting 521
7 Tobacco Regulation in the Twenty-First Century 522
8 Research Challenges Critical to Policy Development and Regulation 523
9 Conclusions 528
References 529
Index 536