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.
Drugs, Addiction, and the Brain explores the molecular, cellular, and neurocircuitry systems in the brain that are responsible for drug addiction. Common neurobiological elements are emphasized that provide novel insights into how the brain mediates the acute rewarding effects of drugs of abuse and how it changes during the transition from initial drug use to compulsive drug use and addiction. The book provides a detailed overview of the pathophysiology of the disease. The information provided will be useful for neuroscientists in the field of addiction, drug abuse treatment providers, and undergraduate and postgraduate students who are interested in learning the diverse effects of drugs of abuse on the brain. - Full-color circuitry diagrams of brain regions implicated in each stage of the addiction cycle- Actual data figures from original sources illustrating key concepts and findings- Introduction to basic neuropharmacology terms and concepts- Introduction to numerous animal models used to study diverse aspects of drug use. - Thorough review of extant work on the neurobiology of addiction
Front Cover 1
Drugs, Addiction, and the Brain 4
Copyright 5
Contents 6
Preface 8
Chapter 1 - What is Addiction? 10
DEFINITIONS OF ADDICTION 10
NEUROADAPTATIONAL VIEWS OF ADDICTION
29
SUMMARY 35
Suggested Reading 36
Chapter 2 - Introduction to the Neuropsychopharmacology of Drug Addiction 38
THE CENTRAL NERVOUS SYSTEM 39
PHARMACOLOGY FOR ADDICTION 42
PHARMACOKINETICS 44
BASIC NEUROBIOLOGY OF ADDICTION 51
BRAIN STRUCTURES AND FUNCTIONS RELEVANT TO THE THREE STAGES OF THE ADDICTION CYCLE 61
NEUROADAPTATIONAL SUMMARY 71
Suggested Reading 72
Chapter 3 - Animal Models of Addiction 74
VALIDATION OF ANIMAL MODELS OF DRUG ADDICTION 76
ANIMAL MODELS OF THE BINGE/INTOXICATION STAGE OF THE ADDICTION CYCLE 77
ANIMAL MODELS OF THE WITHDRAWAL/NEGATIVE AFFECT STAGE OF THE ADDICTION CYCLE 87
ANIMAL MODELS OF THE PREOCCUPATION/ANTICIPATION STAGE OF THE ADDICTION CYCLE 92
ANIMAL MODELS OF VULNERABILITY TO ADDICTION 97
SUMMARY OF ANIMAL MODELS OF ADDICTION 98
Suggested Reading 99
Chapter 4 - Psychostimulants 102
DEFINITIONS 102
HISTORY OF PSYCHOSTIMULANT USE 104
PHYSIOLOGICAL EFFECTS 111
BEHAVIORAL EFFECTS 111
MEDICAL USES 114
PHARMACOKINETICS 114
BEHAVIORAL MECHANISM OF ACTION
117
USE, ABUSE, AND ADDICTION 118
NEUROBIOLOGICAL EFFECTS 121
SUMMARY 139
Suggested Reading 140
Chapter 5 - Opioids 142
DEFINITIONS 142
HISTORY OF OPIOID USE 143
PHYSIOLOGICAL EFFECTS 144
BEHAVIORAL EFFECTS 145
MEDICAL USES 145
PHARMACOKINETICS 148
BEHAVIORAL MECHANISM 149
USE, ABUSE, AND ADDICTION 151
NEUROBIOLOGICAL EFFECTS 163
SUMMARY 179
Suggested Reading 180
Chapter 6 - Alcohol 182
DEFINITIONS 182
HISTORY OF ALCOHOL USE 184
BEHAVIORAL EFFECTS 188
PHARMACOKINETICS 189
USE, ABUSE, AND ADDICTION 191
ALCOHOL TOXICITY 197
BEHAVIORAL MECHANISM OF ACTION 204
NEUROBIOLOGICAL EFFECTS 205
SUMMARY 226
Suggested Reading 227
Chapter 7 - Nicotine 230
DEFINITIONS 230
HISTORY OF USE 231
MEDICAL USE AND BEHAVIORAL EFFECTS 239
PHARMACOKINETICS 240
USE, ABUSE, AND ADDICTION 241
BEHAVIORAL MECHANISM 247
NEUROBIOLOGICAL EFFECTS 248
SUMMARY 267
Suggested Reading 268
Chapter 8 - Cannabinoids 270
DEFINITIONS 270
HISTORY OF CANNABINOID USE 277
MEDICAL USES 278
BEHAVIORAL EFFECTS 280
PHARMACOKINETICS 282
USE, ABUSE, AND ADDICTION 284
BEHAVIORAL MECHANISM OF ACTION 296
NEUROBIOLOGICAL EFFECTS 297
SUMMARY 315
Suggested Reading 316
Chapter 9 - Medications for the Treatment of Addiction – A Neurobiological Perspective 318
CONCEPTUAL APPROACH FOR UNDERSTANDING CURRENT AND FUTURE MEDICATIONS DEVELOPMENT
319
EFFECTS OF KNOWN MEDICATIONS ON ANIMAL MODELS OF ADDICTION – REVERSE VALIDITY (ROSETTA STONE APPROACH) 325
NOVEL TARGETS FOR MEDICATION DEVELOPMENT 331
HUMAN LABORATORY STUDIES 337
INDIVIDUAL DIFFERENCES AND MEDICATION DEVELOPMENT 340
CLINICAL TRIALS – UNIQUE 340
SUMMARY 340
Suggested Reading 341
Index 344
Introduction to the Neuropsychopharmacology of Drug Addiction
Abstract
Drug addiction involves a three-stage cycle – binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation – that worsens over time and involves allostatic changes in the brain reward and stress systems. Two primary sources of reinforcement, positive and negative reinforcement, have been hypothesized to play a role in this allostatic process.
The construct of negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in the brain reward and stress systems. Acute withdrawal from all major drugs of abuse increases reward thresholds, decreases mesolimbic dopamine activity, increases anxiety-like responses, increases extracellular levels of corticotropin-releasing factor (CRF) in the central nucleus of the amygdala, and increases dynorphin in the ventral striatum. Excessive drug taking also activates CRF in the medial prefrontal cortex, paralleled by deficits in executive function that may facilitate the transition to compulsive-like responding.
Keywords
drug addiction; negative reinforcement; reward system; stress system; allostatic process; reward threshold; dopamine; corticotropin-releasing factor; pharmacology; pharmacokinetics; neurobiology of addiction
Outline
Neurons 30
Glia 32
What is a Drug, and What is Pharmacology? 33
Absorption 35
Drug Receptors and Signal Transduction 38
Basic Neurobiology of Addiction 42
Dopamine 42
Corticotropin-Releasing Factor 45
Vasopressin 48
Nociceptin 50
Brain Structures and Functions Relevant to the Three Stages of the Addiction Cycle 52
Binge/Intoxication Stage – Basal Ganglia 52
Withdrawal/Negative Affect Stage – Extended Amygdala 54
“Neuro-,” of or relating to the brain
The Central Nervous System
Neurons
FIGURE 2.1 Anatomy of a neuron.
Neurotransmission
FIGURE 2.2 Neurons, synapses, and neurotransmitters. A typical example is shown for the neurotransmitter dopamine.
FIGURE 2.3 Synaptic neurotransmission. The figure shows a generalized process of synaptic transmission. (1) Various components of the neurotransmission machinery, such as enzymes, proteins, mRNA, and so on (depending on the neurotransmitter in question) are transported down the axon from the cell body. (2) The axonal membrane is electrically excited. (3) Organelles and enzymes in the nerve terminal synthesize, store, and release the neurotransmitter and activate the reuptake process. (4) Enzymes in the extracellular space and within the glia catabolize excess neurotransmitters released from nerve terminals. (5) The postsynaptic receptor triggers the response of the postsynaptic cell to the neurotransmitter. (6) Organelles within postsynaptic cells respond to the receptor trigger. (7) Interactions between genetic expression and postsynaptic nerve cells influence cytoplasmic organelles that respond to neurotransmitter action. (8) Certain steps are modifiable by events that occur at the synaptic contact zone. (9) The electrical portion of the nerve cell membrane integrates postsynaptic potentials in response to various neurotransmitters and produce an action potential. (10) The postsynaptic cell sends an action potential down its axon. (11) The neurotransmitter is released. The neurotransmitter that is released from the nerve terminal can be modulated by autoreceptors that respond to the neurotransmitter. [Modified with permission from Iversen LL, Iversen SD, Bloom FE, Roth RH. Introduction to Neuropsychopharmacology. Oxford, New York, 2009, p. 26.]
Glia
Erscheint lt. Verlag | 12.7.2014 |
---|---|
Sprache | englisch |
Themenwelt | Geisteswissenschaften ► Psychologie ► Persönlichkeitsstörungen |
Geisteswissenschaften ► Psychologie ► Sucht / Drogen | |
Medizin / Pharmazie ► Medizinische Fachgebiete ► Neurologie | |
Medizin / Pharmazie ► Medizinische Fachgebiete ► Psychiatrie / Psychotherapie | |
Medizin / Pharmazie ► Medizinische Fachgebiete ► Suchtkrankheiten | |
Naturwissenschaften ► Biologie ► Humanbiologie | |
Naturwissenschaften ► Biologie ► Zoologie | |
Sozialwissenschaften ► Soziologie | |
ISBN-10 | 0-12-386959-5 / 0123869595 |
ISBN-13 | 978-0-12-386959-3 / 9780123869593 |
Haben Sie eine Frage zum Produkt? |
Größe: 34,1 MB
Kopierschutz: Adobe-DRM
Adobe-DRM ist ein Kopierschutz, der das eBook vor Mißbrauch schützen soll. Dabei wird das eBook bereits beim Download auf Ihre persönliche Adobe-ID autorisiert. Lesen können Sie das eBook dann nur auf den Geräten, welche ebenfalls auf Ihre Adobe-ID registriert sind.
Details zum Adobe-DRM
Dateiformat: PDF (Portable Document Format)
Mit einem festen Seitenlayout eignet sich die PDF besonders für Fachbücher mit Spalten, Tabellen und Abbildungen. Eine PDF kann auf fast allen Geräten angezeigt werden, ist aber für kleine Displays (Smartphone, eReader) nur eingeschränkt geeignet.
Systemvoraussetzungen:
PC/Mac: Mit einem PC oder Mac können Sie dieses eBook lesen. Sie benötigen eine
eReader: Dieses eBook kann mit (fast) allen eBook-Readern gelesen werden. Mit dem amazon-Kindle ist es aber nicht kompatibel.
Smartphone/Tablet: Egal ob Apple oder Android, dieses eBook können Sie lesen. Sie benötigen eine
Geräteliste und zusätzliche Hinweise
Buying eBooks from abroad
For tax law reasons we can sell eBooks just within Germany and Switzerland. Regrettably we cannot fulfill eBook-orders from other countries.
Größe: 20,3 MB
Kopierschutz: Adobe-DRM
Adobe-DRM ist ein Kopierschutz, der das eBook vor Mißbrauch schützen soll. Dabei wird das eBook bereits beim Download auf Ihre persönliche Adobe-ID autorisiert. Lesen können Sie das eBook dann nur auf den Geräten, welche ebenfalls auf Ihre Adobe-ID registriert sind.
Details zum Adobe-DRM
Dateiformat: EPUB (Electronic Publication)
EPUB ist ein offener Standard für eBooks und eignet sich besonders zur Darstellung von Belletristik und Sachbüchern. Der Fließtext wird dynamisch an die Display- und Schriftgröße angepasst. Auch für mobile Lesegeräte ist EPUB daher gut geeignet.
Systemvoraussetzungen:
PC/Mac: Mit einem PC oder Mac können Sie dieses eBook lesen. Sie benötigen eine
eReader: Dieses eBook kann mit (fast) allen eBook-Readern gelesen werden. Mit dem amazon-Kindle ist es aber nicht kompatibel.
Smartphone/Tablet: Egal ob Apple oder Android, dieses eBook können Sie lesen. Sie benötigen eine
Geräteliste und zusätzliche Hinweise
Buying eBooks from abroad
For tax law reasons we can sell eBooks just within Germany and Switzerland. Regrettably we cannot fulfill eBook-orders from other countries.
aus dem Bereich