Behavioral Neuroscience of Drug Addiction (eBook)

7854_1_En_FM1_OnlinePDF 1
7854_1_En_1_Part_OnlinePDF 12
Chapter : 12
7854_1_En_1_Chapter_OnlinePDF 13
Neuroplastic Alterations in the Limbic System Following Cocaine or Alcohol Exposure 13
Introduction 14
Ionotropic Glutamate Receptors 15
Cocaine-Induced Synaptic Plasticity in Midbrain DA Neurons 16
Cocaine-Induced Synaptic Plasticity in the NAc 18
Amygdala Plasticity and Drugs of Abuse 19
Alcohol and Plasticity in Glutamate Receptors 22
Altered Intrinsic Excitability After Alcohol or Cocaine 24
Conclusions and Future Directions 27
References 28
7854_1_En_2_Chapter_OnlinePDF 38
Dopamine Signaling in the Nucleus Accumbens of Animals Self-Administering Drugs of Abuse 38
The Dopamine System: Implication in Normal Behavior and Addiction 40
Drug Addiction and Dopamine Neurotransmission in Humans 40
Drug Self-Administration as an Animal Model for Drug Addiction 40
Drug-Self-Administration and Dopamine in the Nucleus Accumbens 41
Anatomy of the Dopamine System and Dopamine Signal Transduction: Phasic and Tonic Release 42
Proposed Functions of Dopamine in the NAcc 43
Dopamine and Motivated Behavior 43
Dopamine and Reinforcement Learning 44
Dopamine Detection in the Behaving Animal: In Vivo Microdialysis, Chronoamperometry, and Fast-Scan Cyclic Voltammetry (FSCV) 45
In Vivo Microdialysis 45
Electrochemical Techniques 45
In Vivo Chronoamperometry 46
In Vivo FSCV 47
Effects of Drugs of Abuse on Extracellular Dopamine Concentration in the NAcc 47
The Dopamine Hypothesis of Addiction 47
Drug Effects on Dopamine Signaling Measured Over the Course of Minutes: Microdialysis Studies 48
Drug Effects on Dopamine Signaling Measured Over the Course of Seconds to Hours: Chronoamperometry Studies 49
Drug Effects on Dopamine Signaling Measured on a Subsecond Time Scale: FSCV Studies 50
Changes in Phasic Dopamine Signaling to Response-Independent Drug Administration 50
Changes in Phasic Dopamine Signaling During Cocaine Self-Administration: The Role of Operant Behavior and Conditioned Stimuli 52
Summary 55
Effects of Withdrawal from Drugs of Abuse on the NAcc Dopamine System 55
Tonic Dopamine During Withdrawal 56
Phasic Dopamine During (Short-Term) Withdrawal 57
Stimulus-Induced NAcc Dopamine Release in the Absence of Drug: Implications for Reinstatement of Drug Seeking 58
Effects of Drug Cues on Tonic Dopamine Concentration in the NAcc 58
Effects of Drug Cues on Phasic Dopamine Signaling in the NAcc 59
The Role of NAcc Dopamine in Drug Addiction 60
Motivation and Addiction 61
Associative Learning and Addiction 61
Different Functions for Phasic and Tonic Dopamine Transmission in Addiction 62
Dopamine Signaling in the Drug-Naïve State (Fig.2a) 63
Immediate Effects of Drug Exposure (Fig.2b) 63
Long-Term Effects of Drug Exposure During Drug Withdrawal (Fig.2c) 66
Summary 67
References 67
7854_1_En_3_Chapter_OnlinePDF 81
Amygdala Mechanisms of Pavlovian Psychostimulant Conditioning and Relapse 81
Introduction 82
Amygdala Anatomy 84
Intrinsic Circuitry of the Amygdala 84
Afferent/Efferent Amygdala Projections 86
Behavioral Models of Drug Abuse and Relapse 88
Conditioned Place Preference 89
Self-Administration and Reinstatement 90
Summary of Behavioral Findings 92
Amygdala Neuronal Activity and Addiction 92
Immediate Early Gene Expression 93
Electrophysiological Recordings 93
Downstream Signaling Cascades and Neuroadaptations 95
Cellular and Molecular Mechanisms 96
Amygdala Neuroadaptations and Plasticity in Learning 97
Conclusions 98
Summary and Synthesis 98
Future Research 99
Clinical Relevance and Application 100
References 100
7854_1_En_4_Chapter_OnlinePDF 108
Prefrontal Cortical Regulation of Drug Seeking in Animal Models of Drug Relapse 108
Introduction 109
Environmental Stimulus-induced Relapse 110
Relapse Following Extinction 112
Anterior Cingulate and Prelimbic Cortex 112
Infralimbic Cortex 114
Orbitofrontal Cortex 115
Relapse Following Abstinence 115
Anterior Cingulate and Prelimbic Cortex 115
Infralimbic Cortex 116
Orbitofrontal Cortex 116
Drug-primed Relapse 117
Anterior Cingulate and Prelimbic Cortex 117
Infralimbic Cortex 118
Orbitofrontal Cortex 118
Stress-induced Relapse 118
Anterior Cingulate and Prelimbic Cortex 119
Infralimbic Cortex 119
Orbitofrontal Cortex 119
Concluding Remarks 119
References 120
7854_1_En_5_Chapter_OnlinePDF 125
Neural Substrates of Psychostimulant Withdrawal-Induced Anhedonia 125
Introduction: Anhedonia and Psychostimulants 126
Psychostimulant Withdrawal in Humans 128
Theoretical Perspective on Psychostimulant Withdrawal-Induced Anhedonia 131
Psychostimulant Withdrawal-Induced Anhedonia in Animals 132
Assessment of Anhedonia in Animals 133
Assessment of Brain Reward Function with the Intracranial Self-Stimulation Procedure 135
Assessing Decreases in Incentive-Motivation for Rewarding Stimuli 139
Progressive-Ratio Responding for a Natural Reinforcer 139
Sucrose Preference/Consumption 139
Positive and Negative Contrast Procedures 140
Incentive-Motivation for Sexual Reward 141
Novelty-Induced Conditioned Place Preference 142
Neural Substrates and Psychostimulant Withdrawal-Induced Anhedonia 142
Neurotransmitters 146
Dopamine 146
Serotonin 147
Norepinephrine 148
Glutamate 150
GABA 152
Acetylcholine 154
Neurohormones, Neuropeptides, and Neurotrophic Factors 155
Neurosteroids 159
Endocannabinoids 160
Cytokines 160
Summary and Conclusions 161
References 163
7854_1_En_6_Chapter_OnlinePDF 185
7854_1_En_2_Part_OnlinePDF 202
Chapter : 202
7854_1_En_7_Chapter_OnlinePDF 203
Imaging Receptor Changes in Human Drug Abusers 203
Introduction 204
Cocaine 205
Cocaine and the Dopamine Transporter 205
Cocaine and the D2/3 Receptor 206
Cocaine and the Serotonin Transporter 207
Cocaine and the mu-Opioid Receptor 207
Alcohol 208
Alcohol and the D2/3 Receptor 208
Alcohol and the Dopamine Transporter 209
Alcohol and the Serotonin Transporter 210
Alcohol and the mu-Opioid Receptor 211
Alcohol and the GABAA-BZ Receptor 212
Nicotine 213
Nicotine and the beta2-Nicotinic Acetylcholine Receptor (beta2*-nAChR) 213
Nicotine and the D1 Receptor 214
Nicotine and the D2/3 Receptor 214
Nicotine and the Dopamine Transporter 215
Nicotine and the Serotonin Transporter 215
Opiates 215
Opiate Dependence and the mu-Opioid Receptor 215
Opiate Dependence and the D2/3 Receptor 216
Conclusions 216
References 217
7854_1_En_8_Chapter_OnlinePDF 222
7854_1_En_9_Chapter_OnlinePDF 249
Imaging Cognitive Deficits in Drug Abuse 249
Introduction 251
Imaging Cognitive Deficits in Cannabis Users 252
Summary 252
Imaging Cognitive Deficits in Cannabis Users 252
Resting Paradigm 253
Cognitive Challenge Paradigm 253
Extended Washout Period 254
Focus on the Growing Adolescent Brain, Neuroadaptation, Stress, and Dysfunction of Hippocampus and Amygdala 256
Associative Memory 257
Imaging Cognitive Deficits in Amphetamine, Methamphetamine, MDMA, and Cocaine Users 258
Summary 258
Amphetamine and Methamphetamine 259
MDMA 259
Cocaine 260
Imaging Cognitive Deficits in Amphetamine and Methamphetamine Users 260
Imaging Cognitive Deficits in MDMA (3,4-Methylenedioxymethamphetamine, Ecstasy) Users 263
Imaging Cognitive Deficits in Cocaine Users 264
Neuropsychological Findings 264
Imaging Findings 264
Therapy Issues 264
Craving Issues 265
Stress Issues 266
Sex Differences 267
Imaging Cognitive Deficits in Heroin and Methadone use 267
Summary 267
Imaging Cognitive Deficits in Heroin and Methadone Users 268
Heroin 268
Methadone 269
Imaging Prenatal Conditions 270
Summary on Prenatal Children Exposed to Drugs 270
Imaging Cognitive Deficits in Children Exposed to Illicit Drugs 271
References 271
7854_1_En_10_Chapter_OnlinePDF 278
Neural Markers of Genetic Vulnerability to Drug Addiction 278
Introduction 280
Heritability and Epidemiology of Nicotine and Alcohol Dependence 281
Defining Dependence: Clinical Definitions and Complexities in Addiction Studies 281
Dysfunction of the Brain Reward System in Alcohol and Nicotine Dependence - Rationales for Potential Genetic Mechanisms 283
Strategies of Genetic Analyses in Alcohol and Nicotine Dependence: Principles of Genetic Linkage, Candidate Gene/Whole Genome 285
Linkage Studies in Alcohol and Nicotine Dependence 286
Association Studies in Alcohol and Nicotine Dependence 287
Genome-Wide Association Studies in Alcohol and Nicotine Dependence 290
Combined Neuroimaging and Genetics Studies 291
Summary and Outlook 293
References 295
7854_1_En_11_Chapter_OnlinePDF 301
The Role of Executive Control in Human Drug Addiction 301
Introduction 302
Executive Control Processes and Their Constituent Neural Network 303
Neuroanatomy of Executive Control Processes 303
Executive Control Dysfunction in Addicted Drug Users 304
Attentional Bias for Drug-Related Stimuli 305
Executive Control Dysfunction in ``At-Risk´´ Individuals 308
Future Studies 310
References 311
7854_1_En_12_Chapter_OnlinePDF 319
The Behavioral Economics of Drug Dependence: Towards the Consilience of Economics and Behavioral Neuroscience 319
Introduction 320
Introduction to Behavioral Economics of Drug Dependence 320
Demand and Substance Abuse 321
Delay Discounting and Drug Dependence 325
Delay Discounting as a Measure of Time Perception and Temporal Horizon 328
Neural Correlates of Delay Discounting 329
Competing Neurobehavioral Systems and Addiction 331
Conclusion 333
References 334
7854_1_En_13_Chapter_OnlinePDF 342
Novel Pharmacological Approaches to Drug Abuse Treatment 342
Introduction 344
Nicotine 344
Neurobiology 344
Treatment Approaches 345
Withdrawal/Abstinence/Initiation 345
Nicotine Replacement Therapies 345
Nicotinic Receptor Antagonists/Partial Agonists 346
Antidepressants 346
Central Adrenergic Agonists 347
Immunotherapy 348
Other Medications 348
Relapse Prevention 349
Alcohol 349
Neurobiology 349
Treatment Approaches 350
Withdrawal/Abstinence 350
Benzodiazepines and Barbiturates 351
Nonbenzodiazepine GABA Modulators 351
Other Medications 352
Relapse Prevention 352
Glutamate Modulators 352
mu-Opioid Antagonists 353
Serotonergic Modulators 354
Other Medications 355
Cannabis 355
Neurobiology 355
Treatment Approaches 356
Withdrawal/Abstinence Initiation 356
Cannabinoid Receptor Agonists 356
Central Adrenergic Agonists 357
Mood Stabilizers and Antidepressants 357
Relapse Prevention 358
CB1 Antagonists 358
Opioid Antagonists 358
Anandamide Deactivation Inhibitors 358
Other Medications 359
Stimulants 359
Neurobiology 359
Cocaine Treatment Approaches 360
Dopaminergic Agents 360
Adrenergic Antagonists/Central Agonists 362
GABAergic Modulators 362
Glutamatergic Modulators 363
Immunotherapies 364
Other Medications 365
Methamphetamine Treatment Approaches 365
Opioids 366
Neurobiology 366
Treatment Approaches 366
Withdrawal/Abstinence Initiation 366
mu-Opioid Agonists 366
Central Adrenergic Agonists 367
Relapse Prevention 367
mu-Opioid Agonists 367
mu-Opioid Partial Agonist/Antagonist 368
mu-Opioid Antagonists 368
Other Medications 369
Conclusion 369
References 370
7854_1_En_BM2_OnlinePDF 386
: Index 386