Behavioral Neuroscience of Drug Addiction

1. Auflage 2009
ISBN: 978-3-642-03001-7
Verlag: Springer
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 392 Seiten

Drug addiction is a chronically relapsing mental illness involving severe motivational disturbances and loss of behavioral control leading to personal dev- tation. The disorder af?icts millions of people, often co-occurring with other mental illnesses with enormous social and economic costs to society. Several decades of research have established that drugs of abuse hijack the brain’s natural reward substrates, and that chronic drug use causes aberrant alterations in these rewa- processing systems. Such aberrations may be demonstrated at the cellular, neu- transmitter, and regional levels of information processing using either animal models or neuroimaging in humans following chronic drug exposure. Behaviorally, these neural aberrations manifest as exaggerated, altered or dysfunctional expr- sion of learned behavioral responses related to the pursuit of drug rewards, or to environmental factors that precipitate craving and relapse during periods of drug withdrawal. Current research efforts are aimed at understanding the associative and causal relationships between these neurobiological and behavioral events, such that treatment options will ultimately employ therapeutic amelioration of neural de?cits and restoration of normal brain processing to promote efforts to abstain from further drug use. The Behavioral Neuroscience of Drug Addiction, part of the Springer series on Current Topics in Behavioral Neurosciences, contains scholarly reviews by noted experts on multiple topics from both basic and clinical neuroscience ?elds.

Autoren/Hrsg.

Inhaltsverzeichnis

1;7854_1_En_FM1_OnlinePDF;1
2;7854_1_En_1_Part_OnlinePDF;12
2.1;Chapter : ;12
3;7854_1_En_1_Chapter_OnlinePDF;13
3.1;Neuroplastic Alterations in the Limbic System Following Cocaine or Alcohol Exposure;13
3.1.1;Introduction;14
3.1.2;Ionotropic Glutamate Receptors;15
3.1.3;Cocaine-Induced Synaptic Plasticity in Midbrain DA Neurons;16
3.1.4;Cocaine-Induced Synaptic Plasticity in the NAc;18
3.1.5;Amygdala Plasticity and Drugs of Abuse;19
3.1.6;Alcohol and Plasticity in Glutamate Receptors;22
3.1.7;Altered Intrinsic Excitability After Alcohol or Cocaine;24
3.1.8;Conclusions and Future Directions;27
3.1.9;References;28
4;7854_1_En_2_Chapter_OnlinePDF;38
4.1;Dopamine Signaling in the Nucleus Accumbens of Animals Self-Administering Drugs of Abuse;38
4.1.1;The Dopamine System: Implication in Normal Behavior and Addiction;40
4.1.1.1;Drug Addiction and Dopamine Neurotransmission in Humans;40
4.1.1.2;Drug Self-Administration as an Animal Model for Drug Addiction;40
4.1.1.3;Drug-Self-Administration and Dopamine in the Nucleus Accumbens;41
4.1.1.4;Anatomy of the Dopamine System and Dopamine Signal Transduction: Phasic and Tonic Release;42
4.1.1.5;Proposed Functions of Dopamine in the NAcc;43
4.1.1.5.1;Dopamine and Motivated Behavior;43
4.1.1.5.2;Dopamine and Reinforcement Learning;44
4.1.2;Dopamine Detection in the Behaving Animal: In Vivo Microdialysis, Chronoamperometry, and Fast-Scan Cyclic Voltammetry (FSCV);45
4.1.2.1;In Vivo Microdialysis;45
4.1.2.2;Electrochemical Techniques;45
4.1.2.2.1;In Vivo Chronoamperometry;46
4.1.2.2.2;In Vivo FSCV;47
4.1.3;Effects of Drugs of Abuse on Extracellular Dopamine Concentration in the NAcc;47
4.1.3.1;The Dopamine Hypothesis of Addiction;47
4.1.3.2;Drug Effects on Dopamine Signaling Measured Over the Course of Minutes: Microdialysis Studies;48
4.1.3.3;Drug Effects on Dopamine Signaling Measured Over the Course of Seconds to Hours: Chronoamperometry Studies;49
4.1.3.4;Drug Effects on Dopamine Signaling Measured on a Subsecond Time Scale: FSCV Studies;50
4.1.3.4.1;Changes in Phasic Dopamine Signaling to Response-Independent Drug Administration;50
4.1.3.4.2;Changes in Phasic Dopamine Signaling During Cocaine Self-Administration: The Role of Operant Behavior and Conditioned Stimuli;52
4.1.3.5;Summary;55
4.1.4;Effects of Withdrawal from Drugs of Abuse on the NAcc Dopamine System;55
4.1.4.1;Tonic Dopamine During Withdrawal;56
4.1.4.2;Phasic Dopamine During (Short-Term) Withdrawal;57
4.1.5;Stimulus-Induced NAcc Dopamine Release in the Absence of Drug: Implications for Reinstatement of Drug Seeking;58
4.1.5.1;Effects of Drug Cues on Tonic Dopamine Concentration in the NAcc;58
4.1.5.2;Effects of Drug Cues on Phasic Dopamine Signaling in the NAcc;59
4.1.6;The Role of NAcc Dopamine in Drug Addiction;60
4.1.6.1;Motivation and Addiction;61
4.1.6.2;Associative Learning and Addiction;61
4.1.7;Different Functions for Phasic and Tonic Dopamine Transmission in Addiction;62
4.1.7.1;Dopamine Signaling in the Drug-Naïve State (Fig.2a);63
4.1.7.2;Immediate Effects of Drug Exposure (Fig.2b);63
4.1.7.3;Long-Term Effects of Drug Exposure During Drug Withdrawal (Fig.2c);66
4.1.8;Summary;67
4.1.9;References;67
5;7854_1_En_3_Chapter_OnlinePDF;81
5.1;Amygdala Mechanisms of Pavlovian Psychostimulant Conditioning and Relapse;81
5.1.1;Introduction;82
5.1.2;Amygdala Anatomy;84
5.1.2.1;Intrinsic Circuitry of the Amygdala;84
5.1.2.2;Afferent/Efferent Amygdala Projections;86
5.1.3;Behavioral Models of Drug Abuse and Relapse;88
5.1.3.1;Conditioned Place Preference;89
5.1.3.2;Self-Administration and Reinstatement;90
5.1.3.3;Summary of Behavioral Findings;92
5.1.4;Amygdala Neuronal Activity and Addiction;92
5.1.4.1;Immediate Early Gene Expression;93
5.1.4.2;Electrophysiological Recordings;93
5.1.5;Downstream Signaling Cascades and Neuroadaptations;95
5.1.5.1;Cellular and Molecular Mechanisms;96
5.1.5.2;Amygdala Neuroadaptations and Plasticity in Learning;97
5.1.6;Conclusions;98
5.1.6.1;Summary and Synthesis;98
5.1.6.2;Future Research;99
5.1.6.3;Clinical Relevance and Application;100
5.1.7;References;100
6;7854_1_En_4_Chapter_OnlinePDF;108
6.1;Prefrontal Cortical Regulation of Drug Seeking in Animal Models of Drug Relapse;108
6.1.1;Introduction;109
6.1.2;Environmental Stimulus-induced Relapse;110
6.1.2.1;Relapse Following Extinction;112
6.1.2.1.1;Anterior Cingulate and Prelimbic Cortex;112
6.1.2.1.2;Infralimbic Cortex;114
6.1.2.1.3;Orbitofrontal Cortex;115
6.1.2.2;Relapse Following Abstinence;115
6.1.2.2.1;Anterior Cingulate and Prelimbic Cortex;115
6.1.2.2.2;Infralimbic Cortex;116
6.1.2.2.3;Orbitofrontal Cortex;116
6.1.3;Drug-primed Relapse;117
6.1.3.1;Anterior Cingulate and Prelimbic Cortex;117
6.1.3.2;Infralimbic Cortex;118
6.1.3.3;Orbitofrontal Cortex;118
6.1.4;Stress-induced Relapse;118
6.1.4.1;Anterior Cingulate and Prelimbic Cortex;119
6.1.4.2;Infralimbic Cortex;119
6.1.4.3;Orbitofrontal Cortex;119
6.1.5;Concluding Remarks;119
6.1.6;References;120
7;7854_1_En_5_Chapter_OnlinePDF;125
7.1;Neural Substrates of Psychostimulant Withdrawal-Induced Anhedonia;125
7.1.1;Introduction: Anhedonia and Psychostimulants;126
7.1.2;Psychostimulant Withdrawal in Humans;128
7.1.3;Theoretical Perspective on Psychostimulant Withdrawal-Induced Anhedonia;131
7.1.4;Psychostimulant Withdrawal-Induced Anhedonia in Animals;132
7.1.5;Assessment of Anhedonia in Animals;133
7.1.5.1;Assessment of Brain Reward Function with the Intracranial Self-Stimulation Procedure;135
7.1.5.2;Assessing Decreases in Incentive-Motivation for Rewarding Stimuli;139
7.1.5.2.1;Progressive-Ratio Responding for a Natural Reinforcer;139
7.1.5.2.2;Sucrose Preference/Consumption;139
7.1.5.2.3;Positive and Negative Contrast Procedures;140
7.1.5.2.4;Incentive-Motivation for Sexual Reward;141
7.1.5.2.5;Novelty-Induced Conditioned Place Preference;142
7.1.6;Neural Substrates and Psychostimulant Withdrawal-Induced Anhedonia;142
7.1.6.1;Neurotransmitters;146
7.1.6.1.1;Dopamine;146
7.1.6.1.2;Serotonin;147
7.1.6.1.3;Norepinephrine;148
7.1.6.1.4;Glutamate;150
7.1.6.1.5;GABA;152
7.1.6.1.6;Acetylcholine;154
7.1.6.2;Neurohormones, Neuropeptides, and Neurotrophic Factors;155
7.1.6.3;Neurosteroids;159
7.1.6.4;Endocannabinoids;160
7.1.6.5;Cytokines;160
7.1.7;Summary and Conclusions;161
7.1.8;References;163
8;7854_1_En_6_Chapter_OnlinePDF;185
9;7854_1_En_2_Part_OnlinePDF;202
9.1;Chapter : ;202
10;7854_1_En_7_Chapter_OnlinePDF;203
10.1;Imaging Receptor Changes in Human Drug Abusers;203
10.1.1;Introduction;204
10.1.2;Cocaine;205
10.1.2.1;Cocaine and the Dopamine Transporter;205
10.1.2.2;Cocaine and the D2/3 Receptor;206
10.1.2.3;Cocaine and the Serotonin Transporter;207
10.1.2.4;Cocaine and the mu-Opioid Receptor;207
10.1.3;Alcohol;208
10.1.3.1;Alcohol and the D2/3 Receptor;208
10.1.3.2;Alcohol and the Dopamine Transporter;209
10.1.3.3;Alcohol and the Serotonin Transporter;210
10.1.3.4;Alcohol and the mu-Opioid Receptor;211
10.1.3.5;Alcohol and the GABAA-BZ Receptor;212
10.1.4;Nicotine;213
10.1.4.1;Nicotine and the beta2-Nicotinic Acetylcholine Receptor (beta2*-nAChR);213
10.1.4.2;Nicotine and the D1 Receptor;214
10.1.4.3;Nicotine and the D2/3 Receptor;214
10.1.4.4;Nicotine and the Dopamine Transporter;215
10.1.4.5;Nicotine and the Serotonin Transporter;215
10.1.5;Opiates;215
10.1.5.1;Opiate Dependence and the mu-Opioid Receptor;215
10.1.5.2;Opiate Dependence and the D2/3 Receptor;216
10.1.6;Conclusions;216
10.1.7;References;217
11;7854_1_En_8_Chapter_OnlinePDF;222
12;7854_1_En_9_Chapter_OnlinePDF;249
12.1;Imaging Cognitive Deficits in Drug Abuse;249
12.1.1;Introduction;251
12.1.2;Imaging Cognitive Deficits in Cannabis Users;252
12.1.2.1;Summary;252
12.1.2.2;Imaging Cognitive Deficits in Cannabis Users;252
12.1.2.2.1;Resting Paradigm;253
12.1.2.2.2;Cognitive Challenge Paradigm;253
12.1.2.2.3;Extended Washout Period;254
12.1.2.2.4;Focus on the Growing Adolescent Brain, Neuroadaptation, Stress, and Dysfunction of Hippocampus and Amygdala;256
12.1.2.2.5;Associative Memory;257
12.1.3;Imaging Cognitive Deficits in Amphetamine, Methamphetamine, MDMA, and Cocaine Users;258
12.1.3.1;Summary;258
12.1.3.1.1;Amphetamine and Methamphetamine;259
12.1.3.1.2;MDMA;259
12.1.3.1.3;Cocaine;260
12.1.3.2;Imaging Cognitive Deficits in Amphetamine and Methamphetamine Users;260
12.1.3.3;Imaging Cognitive Deficits in MDMA (3,4-Methylenedioxymethamphetamine, Ecstasy) Users;263
12.1.3.4;Imaging Cognitive Deficits in Cocaine Users;264
12.1.3.4.1;Neuropsychological Findings;264
12.1.3.4.2;Imaging Findings;264
12.1.3.4.3;Therapy Issues;264
12.1.3.4.4;Craving Issues;265
12.1.3.4.5;Stress Issues;266
12.1.3.4.6;Sex Differences;267
12.1.4;Imaging Cognitive Deficits in Heroin and Methadone use;267
12.1.4.1;Summary;267
12.1.4.2;Imaging Cognitive Deficits in Heroin and Methadone Users;268
12.1.4.2.1;Heroin;268
12.1.4.2.2;Methadone;269
12.1.5;Imaging Prenatal Conditions;270
12.1.5.1;Summary on Prenatal Children Exposed to Drugs;270
12.1.5.2;Imaging Cognitive Deficits in Children Exposed to Illicit Drugs;271
12.1.6;References;271
13;7854_1_En_10_Chapter_OnlinePDF;278
13.1;Neural Markers of Genetic Vulnerability to Drug Addiction;278
13.1.1;Introduction;280
13.1.2;Heritability and Epidemiology of Nicotine and Alcohol Dependence;281
13.1.3;Defining Dependence: Clinical Definitions and Complexities in Addiction Studies;281
13.1.4;Dysfunction of the Brain Reward System in Alcohol and Nicotine Dependence - Rationales for Potential Genetic Mechanisms;283
13.1.5;Strategies of Genetic Analyses in Alcohol and Nicotine Dependence: Principles of Genetic Linkage, Candidate Gene/Whole Genome;285
13.1.6;Linkage Studies in Alcohol and Nicotine Dependence;286
13.1.7;Association Studies in Alcohol and Nicotine Dependence;287
13.1.8;Genome-Wide Association Studies in Alcohol and Nicotine Dependence;290
13.1.9;Combined Neuroimaging and Genetics Studies;291
13.1.10;Summary and Outlook;293
13.1.11;References;295
14;7854_1_En_11_Chapter_OnlinePDF;301
14.1;The Role of Executive Control in Human Drug Addiction;301
14.1.1;Introduction;302
14.1.2;Executive Control Processes and Their Constituent Neural Network;303
14.1.3;Neuroanatomy of Executive Control Processes;303
14.1.4;Executive Control Dysfunction in Addicted Drug Users;304
14.1.5;Attentional Bias for Drug-Related Stimuli;305
14.1.6;Executive Control Dysfunction in ``At-Risk´´ Individuals;308
14.1.7;Future Studies;310
14.1.8;References;311
15;7854_1_En_12_Chapter_OnlinePDF;319
15.1;The Behavioral Economics of Drug Dependence: Towards the Consilience of Economics and Behavioral Neuroscience;319
15.1.1;Introduction;320
15.1.1.1;Introduction to Behavioral Economics of Drug Dependence;320
15.1.2;Demand and Substance Abuse;321
15.1.3;Delay Discounting and Drug Dependence;325
15.1.4;Delay Discounting as a Measure of Time Perception and Temporal Horizon;328
15.1.5;Neural Correlates of Delay Discounting;329
15.1.6;Competing Neurobehavioral Systems and Addiction;331
15.1.7;Conclusion;333
15.1.8;References;334
16;7854_1_En_13_Chapter_OnlinePDF;342
16.1;Novel Pharmacological Approaches to Drug Abuse Treatment;342
16.1.1;Introduction;344
16.1.2;Nicotine;344
16.1.2.1;Neurobiology;344
16.1.2.2;Treatment Approaches;345
16.1.2.2.1;Withdrawal/Abstinence/Initiation;345
16.1.2.2.1.1;Nicotine Replacement Therapies;345
16.1.2.2.1.2;Nicotinic Receptor Antagonists/Partial Agonists;346
16.1.2.2.1.3;Antidepressants;346
16.1.2.2.1.4;Central Adrenergic Agonists;347
16.1.2.2.1.5;Immunotherapy;348
16.1.2.2.1.6;Other Medications;348
16.1.2.2.2;Relapse Prevention;349
16.1.3;Alcohol;349
16.1.3.1;Neurobiology;349
16.1.3.2;Treatment Approaches;350
16.1.3.2.1;Withdrawal/Abstinence;350
16.1.3.2.1.1;Benzodiazepines and Barbiturates;351
16.1.3.2.1.2;Nonbenzodiazepine GABA Modulators;351
16.1.3.2.1.3;Other Medications;352
16.1.3.2.2;Relapse Prevention;352
16.1.3.2.2.1;Glutamate Modulators;352
16.1.3.2.2.2;mu-Opioid Antagonists;353
16.1.3.2.2.3;Serotonergic Modulators;354
16.1.3.2.2.4;Other Medications;355
16.1.4;Cannabis;355
16.1.4.1;Neurobiology;355
16.1.4.2;Treatment Approaches;356
16.1.4.2.1;Withdrawal/Abstinence Initiation;356
16.1.4.2.1.1;Cannabinoid Receptor Agonists;356
16.1.4.2.1.2;Central Adrenergic Agonists;357
16.1.4.2.1.3;Mood Stabilizers and Antidepressants;357
16.1.4.2.2;Relapse Prevention;358
16.1.4.2.2.1;CB1 Antagonists;358
16.1.4.2.2.2;Opioid Antagonists;358
16.1.4.2.2.3;Anandamide Deactivation Inhibitors;358
16.1.4.2.2.4;Other Medications;359
16.1.5;Stimulants;359
16.1.5.1;Neurobiology;359
16.1.5.2;Cocaine Treatment Approaches;360
16.1.5.2.1;Dopaminergic Agents;360
16.1.5.2.1.1;Adrenergic Antagonists/Central Agonists;362
16.1.5.2.2;GABAergic Modulators;362
16.1.5.2.3;Glutamatergic Modulators;363
16.1.5.2.4;Immunotherapies;364
16.1.5.2.5;Other Medications;365
16.1.5.3;Methamphetamine Treatment Approaches;365
16.1.6;Opioids;366
16.1.6.1;Neurobiology;366
16.1.6.2;Treatment Approaches;366
16.1.6.2.1;Withdrawal/Abstinence Initiation;366
16.1.6.2.1.1;mu-Opioid Agonists;366
16.1.6.2.1.2;Central Adrenergic Agonists;367
16.1.6.2.2;Relapse Prevention;367
16.1.6.2.2.1;mu-Opioid Agonists;367
16.1.6.2.2.2;mu-Opioid Partial Agonist/Antagonist;368
16.1.6.2.2.3;mu-Opioid Antagonists;368
16.1.6.2.2.4;Other Medications;369
16.1.7;Conclusion;369
16.1.8;References;370
17;7854_1_En_BM2_OnlinePDF;386
17.1;: Index;386