Neurobiology of Addiction -  George F. Koob,  Michel Le Moal

Neurobiology of Addiction (eBook)

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2005 | 1. Auflage
504 Seiten
Elsevier Science (Verlag)
978-0-08-049737-2 (ISBN)
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Neurobiology of Addiction is conceived as a current survey and synthesis of the most important findings in our understanding of the neurobiological mechanisms of addiction over the past 50 years. The book includes a scholarly introduction, thorough descriptions of animal models of addiction, and separate chapters on the neurobiological mechanisms of addiction for psychostimulants, opioids, alcohol, nicotine and cannabinoids. Key information is provided about the history, sources, and pharmacokinetics and psychopathology of addiction of each drug class, as well as the behavioral and neurobiological mechanism of action for each drug class at the molecular, cellular and neurocircuitry level of analysis. A chapter on neuroimaging and drug addiction provides a synthesis of exciting new data from neuroimaging in human addicts - a unique perspective unavailable from animal studies. The final chapters explore theories of addiction at the neurobiological and neuroadaptational level both from a historical and integrative perspective.
The book incorporates diverse finding with an emphasis on integration and synthesis rather than discrepancies or differences in the literature.
· Presents a unique perspective on addiction that emphasizes molecular, cellular and neurocircuitry changes in the transition to addiction
· Synthesizes diverse findings on the neurobiology of addiction to provide a heuristic framework for future work
· Features extensive documentation through numerous original figures and tables that that will be useful for understanding and teaching

George F. Koob, Ph.D., received his Bachelor of Science degree from Pennsylvania State University and his Ph.D. in Behavioral Physiology from The Johns Hopkins University. He was recently appointed (in 2014) as Director of the National Institute on Alcohol Abuse and Alcoholism (currently on a leave of absence as Professor at The Scripps Research Institute, Adjunct Professor in the Departments of Psychology and Psychiatry at the University of California San Diego, and Adjunct Professor in the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California San Diego). As an authority on drug addiction and stress, he has contributed to our understanding of the neurocircuitry associated with the acute reinforcing effects of drugs of abuse and the neuroadaptations of the reward and stress circuits associated with the transition to dependence. Dr. Koob has published over 780 scientific papers. In collaboration with Dr. Michel Le Moal, he wrote the renowned book Neurobiology of Addiction (Elsevier, 2006). He was previously Director of the NIAAA Alcohol Research Center at The Scripps Research Institute, Consortium Coordinator for NIAAA's multi-center Integrative Neuroscience Initiative on Alcoholism, and Co-Director of the Pearson Center for Alcoholism and Addiction Research. He has trained 75 postdoctoral fellows and 11 predoctoral fellows. He is currently Editor-in-Chief of the journal Pharmacology Biochemistry and Behavior and Senior Editor for Journal of Addiction Medicine. Dr. Koob taught for 35 years in the Psychology Department at the University of California San Diego, including courses such as Drugs Addiction and Mental Disorders and Impulse Control Disorders, courses that regularly matriculated 400-500 students each. He also taught Contemporary Topics in Central Nervous System Pharmacology at the Skaggs School of Pharmacy and Pharmaceutical Sciences at UCSD for 9 years.
Dr. Koob's research interests have been directed at the neurobiology of emotion, with a focus on the theoretical constructs of reward and stress. He has made contributions to our understanding of the anatomical connections of the emotional systems and the neurochemistry of emotional function. Dr. Koob has identified afferent and efferent connections of the basal forebrain (extended amygdala) in the region of the nucleus accumbens, bed nucleus of the stria terminalis, and central nucleus of the amygdala in motor activation, reinforcement mechanisms, behavioral responses to stress, drug self-administration, and the neuroadaptation associated with drug dependence.
Dr. Koob also is one of the world's authorities on the neurobiology of drug addiction. He has contributed to our understanding of the neurocircuitry associated with the acute reinforcing effects of drugs of abuse and more recently on the neuroadaptations of these reward circuits associated with the transition to dependence. He has validated key animal models for dependence associated with drugs of abuse and has begun to explore a key role of anti-reward systems in the development of dependence.
Dr. Koob's work with the neurobiology of stress includes the characterization of behavioral functions in the central nervous system for catecholamines, opioid peptides, and corticotropin-releasing factor. Corticotropin-releasing factor, in addition to its classical hormonal functions in the hypothalamic-pituitary-adrenal axis, is also located in extrahypothalamic brain structures and may have an important role in brain emotional function. Recent use of specific corticotropin-releasing factor antagonists suggests that endogenous brain corticotropin-releasing factor may be involved in specific behavioral responses to stress, the psychopathology of anxiety and affective disorders, and drug addiction.
Neurobiology of Addiction is conceived as a current survey and synthesis of the most important findings in our understanding of the neurobiological mechanisms of addiction over the past 50 years. The book includes a scholarly introduction, thorough descriptions of animal models of addiction, and separate chapters on the neurobiological mechanisms of addiction for psychostimulants, opioids, alcohol, nicotine and cannabinoids. Key information is provided about the history, sources, and pharmacokinetics and psychopathology of addiction of each drug class, as well as the behavioral and neurobiological mechanism of action for each drug class at the molecular, cellular and neurocircuitry level of analysis. A chapter on neuroimaging and drug addiction provides a synthesis of exciting new data from neuroimaging in human addicts - a unique perspective unavailable from animal studies. The final chapters explore theories of addiction at the neurobiological and neuroadaptational level both from a historical and integrative perspective. The book incorporates diverse finding with an emphasis on integration and synthesis rather than discrepancies or differences in the literature.* Presents a unique perspective on addiction that emphasizes molecular, cellular and neurocircuitry changes in the transition to addiction * Synthesizes diverse findings on the neurobiology of addiction to provide a heuristic framework for future work * Features extensive documentation through numerous original figures and tables that that will be useful for understanding and teaching

Front Cover 1
Neurobiology of Addiction 4
Copyright Page 5
Contents 8
Preface 10
Acknowledgments 12
Chapter 1. What is Addiction 14
Definitions of addiction 14
Neuroadaptational Views of Addiction 23
Summary 32
References 32
Chapter 2. Animal Models of Drug Addiction 36
Definitions and Validation of Animal Models 36
Animal Models for the Binge/Intoxication Stage of the Addiction Cycle 39
Animal Models for the Drug Withdrawal/Negative Affect Stage of the Addiction Cycle 51
Animal Models for the Preoccupation/Anticipation (Craving) Stage of the Addiction Cycle 54
Animal Models for the Transition to Addiction 63
Summary 73
References 73
Chapter 3. Psychostimulants 82
Definitions 82
History of Psychostimulant Use, Abuse, and Addiction 84
Behavioral Effects and Medical Uses 87
Pharmacokinetics 91
Abuse and Addiction Potential 92
Behavioral Mechanisms 95
Neurobiological Mechanism—Neurocircuitry 96
Neurobiological Mechanism—Cellular 109
Neurobiological Mechanism—Molecular 116
Summary 121
References 122
Chapter 4. Opioids 134
Definitions 134
History of Opioid Use, Abuse, and Addiction 134
Medical Use and Behavioral Effects 135
Pharmacokinetics 137
Abuse and Addiction Potential 139
Behavioral Mechanism of Action 147
Neurobiological Mechanism—Neurocircuitry 148
Neurobiological Mechanism—Cellular 163
Neurobiological Mechanism—Molecular 167
Summary 172
References 172
Chapter 5. Alcohol 186
Definitions 186
History of Alcohol Use, Abuse, and Alcoholism 187
Behavioral Effects of Alcohol 188
Pharmacokinetics 191
Abuse and Addiction Potential 194
Behavioral Mechanism of Action 203
Neurobiological Mechanism—Neurocircuitry 204
Neurobiological Mechanism—Cellular 219
Neurobiological Mechanism—Molecular 224
Summary 234
References 234
Chapter 6. Nicotine 256
Definitions 256
History of Tobacco Use, Abuse, and Addiction 257
Medical Use and Behavioral Effects 261
Pharmacokinetics 264
Abuse and Addiction Potential 266
Behavioral Mechanism of Action 271
Neurobiological Mechanism—Neurocircuitry 273
Neurobiological Mechanism—Cellular 281
Neurobiological Mechanism—Molecular 283
Summary 288
References 289
Chapter 7. Cannabinoids 302
Definitions 302
History of Cannabinoid Use, Abuse, and Addiction 306
Medical Use and Behavioral Effects 309
Pharmacokinetics 312
Cannabinoid Tolerance 313
Cannabinoid Withdrawal 314
Pathology and Psychopathology 317
Behavioral Mechanism of Action 320
Neurobiological Mechanism—Neurocircuitry 320
Neurobiological Mechanism—Cellular 329
Neurobiological Mechanism—Molecular 334
Summary 336
References 338
Chapter 8. Imaging 352
Introduction 352
Basic Technical Principles of Neuroimaging 353
Brain Imaging of Drug Addiction 356
Integration of Imaging Studies in Humans with the Neurocircuitry of Addiction 374
Summary 381
References 382
Chapter 9. Neurobiological Theories of Addiction 390
Introduction 391
Neurocircuitry Hypotheses of Addiction Dopamine and Reward 391
Neurocircuitry Theories of Addiction—Executive Function 394
Neurocircuitry Theories of Addiction—Relapse 400
Neurocircuitry Theories of Addiction—Reward and Stress 407
Cellular Hypotheses of Addiction 418
Molecular Hypotheses of Addiction 421
Synthesis: Common Elements of Most Neurobiological Models of Addiction 427
References 429
Chapter 10. Drug Addiction: Transition from Neuroadaptation to Pathophysiology 442
Common Neurobiological Elements in Addiction 442
Overall Conclusions—Neurobiology of Addiction 447
Homeostasis versus Allostasis in Addiction 448
Drug-Seeking to Addiction—An Allostatic View 450
The Allostatic View versus Incentive Sensitization View 457
A NonDopamine-centric View of Addiction 460
Pain and Addiction 461
Neurocircuitry of Compulsive Drug-Seeking and Drug-Taking 463
Implications of the Allostatic View for Motivation and Psychopathology 466
References 466
Appendix 1. Psychostimulants 476
Appendix 2. Opioids 484
Appendix 3. Alcohol 486
Appendix 4. Nicotine 494
Appendix 5. Cannabinoids 496
Index 498

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