Now, in one volume, the latest research from the areas of molcular biology, neurochemistry and behavior analysis of drug abuse and dependence, with, wherever possible, an integration of the data from these various levels of analysis. The ensuing reports point to the complexity of the phenomenon of abuse and dependence and clearly demonstrate that it is determined by a variety of variables from molecular biology and genetics through behavioral history. This complexity is shown, however, to be responsive to rigorous scientific analysis and our success to date gives rise to hope that this distressing public health problem can ultimately be brought under control. Each of the chapters is written by a leading researcher in the field.
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I. Research in the Study of Drug Action and Addiction.- 1 Genetic Vulnerability to Substance Abuse.- A. Heterogeneity of Drug Abuse.- I. Etiological Influences.- 1. Risk Factors.- 2. Genetic Influences.- B. Clinical Studies.- I. Family Genetic Studies.- 1. Alcoholism.- 2. Other Drug Abuse.- II. Levels of Genetic Analysis.- 1. Factors Affecting Use.- 2. Metabolism.- 3. Subjective and Objective Effects.- 4. Drug Specificity.- 5. Alternative Modes of Transmission.- 6. Phenecopies.- C. Molecular Studies.- I. Selecting Genetic Markers.- II. Linkage Analysis.- 1. Dopamine D2 Receptor Locus.- 2. Other Genes.- D. Animal Studies.- I. Animal Models of Drug Taking Behavior.- 1. Behavioral Pharmacology Approach.- 2. Behavioral Genetics Approach.- II. Genetic Variation in Drug Self-Administration and Drug-Reinforced Behavior.- 1. Two-Bottle Choice.- 2. Conditioned Place Preference.- 3. Intracranial Self-Stimulation.- 4. Operant Self-Administration.- III. Drug-Naive Behaviors as Predictors of Vulnerability.- IV. Neurobiological Markers as Predictors of Vulnerability.- V. Response to Abused Drugs as Predictors of Vulnerability.- E. Summary.- References.- 2 Integrative Neurobehavioral Pharmacology: Focus on Cocaine.- A. Introduction.- B. Approaches to Drug Abuse and Dependence.- C. A Cocaine Receptor.- I. Behavioral Models for Drug Abuse.- 1. Drug Self-Administration.- 2. Place Preference.- 3. Alteration of Threshold for Electrical Brain Stimulation Reinforcement.- 4. Drugs of Abuse and Endogenous Reward Systems.- II. Receptor Binding.- III. Interdisciplinary Support for a Dopamine Hypothesis.- D. Brain Imaging.- E. Molecular Actions of Cocaine.- I. Cloning the Dopamine Transporter/Cocaine Receptor.- II. Effects of Chronic Cocaine Administration and Withdrawal.- F. Conclusions.- References.- II. Molecular, Behavioral, and Human Pharmacology of Dependence and Consequences.- 3 Marihuana.- A. Introduction.- B. Cellular and Molecular Effects.- I. Neurochemistry.- 1. Effects on Neurotransmitters.- 2. Receptors.- 3. Second Messenger and Other Transduction Mechanisms.- 4. Integration of Systems.- C. General Pharmacology.- I. Pharmacokinetics.- 1. Absorption and Distribution.- 2. Metabolism and Excretion.- 3. Relationship of THC Levels to Effects.- II. Effects on Organ Systems.- 1. Brain.- 2. Immune System.- 3. Endocrine.- 4. Cardiovascular.- 5. Gastrointestinal.- 6. Renal.- III. Toxicity.- 1. Respiratory Effects.- 2. Psychotic Episodes.- 3. Neurochemical and Histological Effects.- IV. Tolerance.- 1. Animals.- 2. Humans.- V. Dependence.- 1. Animals.- 2. Humans.- VI. ?9-THC During Pregnancy.- 1. Effect on Dams and Litters.- 2. Developmental Toxicity.- 3. Neural Development.- 4. Teratogenecity.- 5. Fetotoxicity - Interactions with Ethanol.- D. Behavioral Pharmacology.- I. Unlearned Behaviors/Ethology.- l. General Comments.- 2. Consummatory Behavior.- 3. Motor Behavior.- 4. Social Behavior.- II. Conditioned Effects.- 1. Drug Discrimination.- 2. Self-Administration.- 3. Performance, Memory and Learning.- E. Conclusions.- References.- 4 Cocaine.- A. History and Epidemiology.- B. General Pharmacology.- I. Pharmacokinetics.- II. Organ and System Toxicity.- III. Fetal and Developmental Toxicity.- IV. Behavioral Toxicity.- C. Neurobiology of Cocaine's Behavioral Effects.- I. Receptor Targets.- II. Sensitization.- III. Reinforcement.- IV. Medications Development.- D. Final Comments.- References.- 5 Opioid Analgesics.- A. Background.- B. Cellular and Molecular Effects.- I. Opioid Receptors.- 1. Early Discoveries.- 2. Opioid Receptor Multiplicity.- 3. Selective Opioid Agonists and Antagonists.- 4. Distribution.- II. Postreceptor Events.- C. General Pharmacology.- I. Pharmacokinetics and Metabolism.- II. General Effects.- III. Immune Function.- IV. Analgesia.- 1. Clinical Observations.- 2. Mechanism of Action of Mu Agonists.- 3. Kappa and Delta Agonists.- V. Tolerance.- VI. Physical Dependence.- D. Behavioral Pharmacology.- I. Reinforcing Effects.- 1. Self-Administration and Place Preference.- 2. Neurobiological Mechanisms.- II. Discriminative Stimulus Characteristics.- III. Schedule-Controlled Behavior.- IV. Conditioned Drug Effects.- V. Learning and Memory.- VI. Unlearned Behaviors.- E. Summary.- References.- 6 Phencyclidine: A Drug of Abuse and a Tool for Neuroscience Research.- A. Introduction and History.- B. Overview of Pharmacological Profile.- I. Humans.- II. Animals.- C. Cellular Mechanisms of Action.- I. The Phencyclidine Receptor.- II. Phencyclidine and the Sigma Binding Site.- III. Phencyclidine and the NMDA Receptor Complex.- IV. Behavioral Correlates of Phencyclidine/NMDA Interactions.- V. Phencyclidine and Dopaminergic Effects -Direct or Indirect Interactions?.- D. Behavioral Pharmacology of Phencyclidine Abuse.- I. Discriminative Stimulus Effects.- II. Self-Administration.- III. Tolerance and Dependence.- IV. Modification of Drug Tolerance and Dependence.- V. Learning and Memory.- E. Concluding Remarks.- References.- 7 Benzodiazepine Discontinuation Syndromes: Clinical and Experimental Aspects.- A. Clinical Aspects of Benzodiazepine Discontinuation.- I. Risk Factors for Benzodiazepine Discontinuation Effects.- 1. Benzodiazepine Compounds.- 2. Dose.- 3. Duration.- 4. Personality Type.- II. Clinical Benzodiazepine Discontinuation Effects.- B. Laboratory Aspects of Benzodiazepine Discontinuation.- I. Behavioral Pharmacology.- II. Neurochemical Effects.- C. Conclusion.- References.- 8 Nicotine.- A. Introduction.- B. Abuse and Dependence in Humans.- I. Epidemiology.- II. Clinical Aspects and Pathophysiology of Nicotine Dependence.- III. Tolerance and Physical Dependence.- C. General Pharmacology.- I. Chemistry and Pharmacokinetics.- 1. Absorption.- 2. Distribution.- 3. Systemic Metabolism.- 4. Brain Metabolic Activity.- 5. Drug Interactions.- II. Pharmacodynamics.- 1. Cardiovascular Effects.- 2. Electroencephalograph Effects.- III. Systemic Effects.- 1. Immunologic Effects.- 2. Hormonal Effects.- 3. Toxicity.- IV. Abuse Liability and Dependence Potential.- 1. Discriminative Effects.- 2. Reinforcing Effects.- 3. Physical Dependence.- D. Neuropharmacology.- I. Nicotinic Receptors.- 1. Receptor Diversity.- 2. Receptor Regulation.- II. Cellular Mechanisms.- 1. Effects of Nicotine on Cell Firing.- 2. Effects of Nicotine on Nerve Terminals.- 3. Effects of Nicotine on Transmitter Release in the Whole Animal.- III. Neuronal Activity and Mechanisms of Reinforcement.- 1. Mesolimbic Dopamine.- 2. Dorsal Noradrenergic Bundle.- 3. Thalamocortical Projections.- 4. Habenulo-Interpeduncular System.- 5. 5-HT Release.- 6. Amino Acid Neurotransmitter Release.- 7. Acetylcholine Release.- 8. Other Measures of Neuronal Activity.- 9. Peripheral Effects.- E. Implications for Medications Development and Conclusions.- References.- 9 Caffeine Reinforcement, Discrimination, Tolerance and Physical Dependence in Laboratory Animals and Humans.- A. Introduction.- B. Reinforcing Effects of Caffeine in Laboratory Animals.- C. Reinforcing Effects of Caffeine in Humans.- D. Discriminative Stimulus Effects of Caffeine in Laboratory Animals.- I. Pharmacologic Mechanisms in Drug Discrimination.- E. Subjective and Discriminative Stimulus Effects of Caffeine in Humans.-…