Koob / Arends BS / Le Moal Drugs, Addiction, and the Brain

1. Auflage 2014
ISBN: 978-0-12-386959-3
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 350 Seiten

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

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.

Autoren/Hrsg.

Koob, George F.

Arends BS, Michael A.

Le Moal, Michel

Inhaltsverzeichnis

1;Front Cover;1
2;Drugs, Addiction, and the Brain;4
3;Copyright;5
4;Contents;6
5;Preface;8
6;Chapter 1 - What is Addiction?;10
6.1;DEFINITIONS OF ADDICTION;10
6.2;NEUROADAPTATIONAL VIEWS OF ADDICTION
;29
6.3;SUMMARY;35
6.4;Suggested Reading;36
7;Chapter 2 - Introduction to the Neuropsychopharmacology of Drug Addiction;38
7.1;THE CENTRAL NERVOUS SYSTEM;39
7.2;PHARMACOLOGY FOR ADDICTION;42
7.3;PHARMACOKINETICS;44
7.4;BASIC NEUROBIOLOGY OF ADDICTION;51
7.5;BRAIN STRUCTURES AND FUNCTIONS RELEVANT TO THE THREE STAGES OF THE ADDICTION CYCLE;61
7.6;NEUROADAPTATIONAL SUMMARY;71
7.7;Suggested Reading;72
8;Chapter 3 - Animal Models of Addiction;74
8.1;VALIDATION OF ANIMAL MODELS OF DRUG ADDICTION;76
8.2;ANIMAL MODELS OF THE BINGE/INTOXICATION STAGE OF THE ADDICTION CYCLE;77
8.3;ANIMAL MODELS OF THE WITHDRAWAL/NEGATIVE AFFECT STAGE OF THE ADDICTION CYCLE;87
8.4;ANIMAL MODELS OF THE PREOCCUPATION/ANTICIPATION STAGE OF THE ADDICTION CYCLE;92
8.5;ANIMAL MODELS OF VULNERABILITY TO ADDICTION;97
8.6;SUMMARY OF ANIMAL MODELS OF ADDICTION;98
8.7;Suggested Reading;99
9;Chapter 4 - Psychostimulants;102
9.1;DEFINITIONS;102
9.2;HISTORY OF PSYCHOSTIMULANT USE;104
9.3;PHYSIOLOGICAL EFFECTS;111
9.4;BEHAVIORAL EFFECTS;111
9.5;MEDICAL USES;114
9.6;PHARMACOKINETICS;114
9.7;BEHAVIORAL MECHANISM OF ACTION
;117
9.8;USE, ABUSE, AND ADDICTION;118
9.9;NEUROBIOLOGICAL EFFECTS;121
9.10;SUMMARY;139
9.11;Suggested Reading;140
10;Chapter 5 - Opioids;142
10.1;DEFINITIONS;142
10.2;HISTORY OF OPIOID USE;143
10.3;PHYSIOLOGICAL EFFECTS;144
10.4;BEHAVIORAL EFFECTS;145
10.5;MEDICAL USES;145
10.6;PHARMACOKINETICS;148
10.7;BEHAVIORAL MECHANISM;149
10.8;USE, ABUSE, AND ADDICTION;151
10.9;NEUROBIOLOGICAL EFFECTS;163
10.10;SUMMARY;179
10.11;Suggested Reading;180
11;Chapter 6 - Alcohol;182
11.1;DEFINITIONS;182
11.2;HISTORY OF ALCOHOL USE;184
11.3;BEHAVIORAL EFFECTS;188
11.4;PHARMACOKINETICS;189
11.5;USE, ABUSE, AND ADDICTION;191
11.6;ALCOHOL TOXICITY;197
11.7;BEHAVIORAL MECHANISM OF ACTION;204
11.8;NEUROBIOLOGICAL EFFECTS;205
11.9;SUMMARY;226
11.10;Suggested Reading;227
12;Chapter 7 - Nicotine;230
12.1;DEFINITIONS;230
12.2;HISTORY OF USE;231
12.3;MEDICAL USE AND BEHAVIORAL EFFECTS;239
12.4;PHARMACOKINETICS;240
12.5;USE, ABUSE, AND ADDICTION;241
12.6;BEHAVIORAL MECHANISM;247
12.7;NEUROBIOLOGICAL EFFECTS;248
12.8;SUMMARY;267
12.9;Suggested Reading;268
13;Chapter 8 - Cannabinoids;270
13.1;DEFINITIONS;270
13.2;HISTORY OF CANNABINOID USE;277
13.3;MEDICAL USES;278
13.4;BEHAVIORAL EFFECTS;280
13.5;PHARMACOKINETICS;282
13.6;USE, ABUSE, AND ADDICTION;284
13.7;BEHAVIORAL MECHANISM OF ACTION;296
13.8;NEUROBIOLOGICAL EFFECTS;297
13.9;SUMMARY;315
13.10;Suggested Reading;316
14;Chapter 9 - Medications for the Treatment of Addiction – A Neurobiological Perspective;318
14.1;CONCEPTUAL APPROACH FOR UNDERSTANDING CURRENT AND FUTURE MEDICATIONS DEVELOPMENT
;319
14.2;EFFECTS OF KNOWN MEDICATIONS ON ANIMAL MODELS OF ADDICTION – REVERSE VALIDITY (ROSETTA STONE APPROACH);325
14.3;NOVEL TARGETS FOR MEDICATION DEVELOPMENT;331
14.4;HUMAN LABORATORY STUDIES;337
14.5;INDIVIDUAL DIFFERENCES AND MEDICATION DEVELOPMENT;340
14.6;CLINICAL TRIALS – UNIQUE;340
14.7;SUMMARY;340
14.8;Suggested Reading;341
15;Index;344

Leseproben

Chapter 2 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 The Central Nervous System 30 Neurons 30 Neurotransmission 31 Glia 32 Pharmacology for Addiction 33 What is a Drug, and What is Pharmacology? 33 Drug Nomenclature 33 Drug Classification 34 Pharmacokinetics 35 Absorption 35 Drug Elimination 36 Drug Receptors and Signal Transduction 38 Dose-Response Functions 40 Therapeutic Ratio 41 Basic Neurobiology of Addiction 42 Dopamine 42 Norepinephrine 43 Opioid Peptides 44 Corticotropin-Releasing Factor 45 Vasopressin 48 Neuropeptide Y 49 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 Preoccupation/Anticipation Stage – Prefrontal Cortex 59 Neuroadaptational Summary 62 Suggested Reading 63 “Neuro-,” of or relating to the brain The brain is not simply an amorphous mass of grayish tissue. It courses with blood and electrical impulses. It regulates the body’s temperature. It tells us how we feel. It allows us to interact with others and the world. It says when to wake up and when to fall asleep. It helps us put our shoes on in the morning. It also is susceptible to a host of external influences, including drugs. To better understand the subsequent chapters in this book and to put the medical, biological, and neurobiological mechanisms of drug addiction into context, we must take a step back to define and explain the common components of the body’s central nervous system, from the macro (brain regions) to the micro (neurons, neurotransmitters). Armed with this information, students will be able to appreciate the in-depth knowledge that has been gained from extensive scientific research during the past 100 years, with the hope that they, too, will be able to discover greater intricacies to explain why many individuals succumb to drug addiction. The Central Nervous System
The human brain consists of two types of cells: roughly 100 billion neurons and a greater number of glia. Neurons are highly specialized cells that have an important and unique functional property that is not shared with any other cells in the body. Neurons communicate with each other through both electrical and chemical mechanisms. More importantly for the theme of this book, neurons communicate through circuits, and these circuits form the structural bases of feelings, thoughts, and behavior, the ultimate functional output of the brain. Neurons
Neurons have four major components: (1) cell body, (2) axons, (3) dendrites, and (4) synapses (Figure 2.1). The cell body contains the nucleus and receives inputs, providing the machinery for the generation of neurotransmitters and action potentials. An action potential occurs when a neuron’s membrane is depolarized beyond its threshold. This depolarization is propagated along the axon. The axon is the “sending” part of the neuron, and it conducts these action potentials to the synapse to release neurotransmitters. The synapse is a specialized space or contact zone between neurons that allows interneuronal communication. One or more dendrites comprise the “receiving” part of the neuron, providing a massive receptive area for the neuronal surface (Figure 2.2). Neurons act on other neurons to exert three major functions: inhibition, excitation, and neuromodulation. Inhibition means that one neuron inhibits another neuron, often through the release of an inhibitory neurotransmitter at the synapse. Excitation means that one neuron activates another neuron through the release of an excitatory neurotransmitter at the synapse. Neuromodulation means that a neuron influences neurotransmission, often at a long distance.
FIGURE 2.1 Anatomy of a neuron. Neurotransmission
The communication between neurons can be distilled into six major steps of neurotransmission relevant to the neuropharmacology of addiction (Figure 2.3). Step 1: Neurotransmitter synthesis, involving the molecular mechanisms of peptide precursors and enzymes for further synthesis or cleavage. Step 2: Neurotransmitter storage. Step 3: Neurotransmitter release from the axon terminal into the synaptic cleft (or from a secreting dendrite some cases). Step 4: Neurotransmitter inactivation caused by removal from the synaptic cleft through a reuptake process, or neurotransmitter breakdown by enzymes in the synapse or presynaptic terminal. Step 5: Activation of the postsynaptic receptor, triggering a response of the postsynaptic cell. Step 6: Subsequent signal transduction that responds to neurotransmitter receptor activation. Drugs of abuse or drugs that counteract the effects of drugs of abuse can interact at any of these steps to dramatically or subtly alter chemical transmission to dysregulate or re-regulate, respectively, homeostatic function.
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
In addition to neurons, the central nervous system contains supporting cells. Supporting cells, generically called glia, can outnumber neurons by a factor of ten. Historically, glia were defined as the “nerve glue” that holds neurons together in the central nervous system. However, glia are now known to have key dynamic functions in the central nervous system, from myelin synthesis, to synapses, to serving as the innate brain defensive system against pathology. Glia consist of three types of supporting cells: oligodendrocytes, astrocytes, and microglia. Oligodendrocytes synthesize myelin and provide an expedient way, via the myelin sheath, to significantly increase how fast an axon can conduct an action potential. Myelin is a long plasma membrane sheet that wraps around...