The Biology of Alcoholism

of Volume 7.- 1 Genetic Factors in Alcohol Abuse: Animal Models.- Animal Models in Alcohol Research.- The Issue of Comprehensiveness.- The Issue of Phylogenetic Generalizability.- A Quantitative Genetic Model.- Some Basic Definitions.- Polygenic Influence.- Genetically Defined Populations in Alcohol Research.- Inbred Strains.- Heterogeneous Populations.- Selective Breeding.- General Principles.- Summary.- References.- 2 Genetic Factors in Alcoholism.- Common Methodological Problems in Research on Genetic.- Factors in Alcoholism.- Diagnosis.- Nosology.- Age of Onset.- Sex Differences.- Family Studies.- Twin Studies.- Adoption Studies.- Association and Linkage Studies.- Models of Transmission.- What Is Transmitted Genetically to Account for Development of Alcoholism.- References.- 3 Acute Pharmacological Actions of Ethanol on the Central Nervous System.- Membranes.- Membranes as Sites for Ethanol Action.- Membrane-bound Enzymes: Regulation of Ion Permeability and Negative Charge.- Effects of Ethanol on Brain Calcium.- Calcium Content, Binding, and Fluorescence Probe Analysis.- Calcium and Behavioral Response to Ethanol.- Calcium Transport in Synaptic Nerve Endings.- Calcium-dependent Membrane ATPase.- Membrane-dependent Neurotransmitter Activity.- Role of Calcium as a Central Messenger.- Effects of Ethanol on Neurotransmitter Systems.- Summary.- References.- 4 Ethanol and Brain Mechanisms of Reward.- Substrates of Brain Stimulation Reward.- Anatomy.- Pharmacology.- Other Considerations.- Substrates of Drug Reward.- Psychomotor Stimulants.- Opiates.- Ethanol.- Interactions of Drugs of Abuse with Brain-Stimulation Reward.- Psychomotor Stimulants.- Opiates.- Ethanol.- Speculations.- Dopamine Pathways of Reward, Memory Formation, and Ethanol.- Anxiety and Ethanol.- References.- 5 Ethanol as a Reinforcer: Comparison with Other Drugs.- Intravenous Drugs as Reinforcers.- Continuous Reinforcement Schedules.- Effects of Drug Deprivation.- Ratio Schedules: Substitution Procedures.- Intragastric Drug Self-administration.- Ethanol and Other Drugs as Reinforcers by the Oral Route.- Drinking of Drug Solutions in the Absence of Inducing Conditions.- Inducing Schedules of Drug Overdrinking.- Oral Drugs as Reinforcers.- Summary and Conclusions.- References.- 6 A Behavioral Analysis of the Reinforcing Properties of Alcohol and Other Drugs in Man.- Reinforcement and the Analysis of Behavior.- Clinical Research on Drug Effects.- Behavioral Effects of Alcohol and Drugs.- Drug Effects in Naive Users.- Clinical Studies of Alcohol Use and Abuse.- Clinical Studies of Opiate Use and Abuse.- Clinical Studies of Stimulant Use and Abuse.- Conclusions: Behavioral Effects of Alcohol and Drugs.- Control of Behavior by Aversive Consequences.- Narcotic Antagonist Self-administration.- Electric Shock Self-administration.- Implications of the Control of Behavior by Aversive Consequences.- Substance Abuse: Similarities and Differences.- Stimulus Self-administration: A Hypothesis.- Biological Consequences of Drug and Alcohol Use.- Conclusions.- References.- 7 Neurochemical Aspects of Tolerance to and Physical Dependence on Alcohol.- Definitions of Functional Tolerance and Dependence.- Factors Modulating Ethanol Tolerance Development.- Effects of Ethanol Administration on Neurotransmitters.- Catecholamine Systems.- Serotonergic Systems.- Cholinergic Systems.- GABA and Glutamate Metabolism.- Cyclic Nucleotides.- Calcium Metabolism.- Neurotransmitter Receptors.- Role of Neuronal Membranes in Development of Tolerance and Dependence.- Role of Condensation Products in Ethanol Tolerance and Dependence.- Conclusions.- References.- 8 Metabolic Mechanisms in Tolerance and Physical Dependence on Alcohol.- Metabolic Tolerance.- Adaptive Changes in the Rate of Ethanol Elimination.- Adaptive Changes in Acetaldehyde Metabolism.- Adaptive Changes in the Redox State.- Metabolism Mechanisms in Physical Dependence.- Metabolism of Ethanol in Brain.- Reactions of Aldehydes.- References.- 9 Endocrine Mechanisms in Tolerance to and Dependence on Alcohol.- Preface.- Conceptual and Methodological Issues.- Alcohol-Endocrine Interactions.- Hypothalamic-Pituitary-Gonadal Axis.- Hypothalamic-Pituitary-Adrenal Axis.- Hypothalamic-Pituitary-Thyroid Axis.- Growth Hormone.- Prolactin.- Vasopressin.- Oxytocin.- Conclusions.- References.- 10 The Relationship of Tolerance and Physical Dependence to Alcohol Abuse and Alcohol Problems.- A Consideration of the Regulation of Alcohol Consumption.- Tolerance.- Definition of Tolerance.- Empirical Studies Bearing on the Relationship of Tolerance to Alcohol Consumption and Alcoholism.- Initial Differences in Tolerance.- Acquired Differences in Tolerance.- Summary and Implications of Knowledge Concerning Tolerance.- Physical Dependence.- Definition of Physical Dependence.- Empirical Studies Bearing on the Relationship of Physical Dependence to Alcohol Consumption and Alcoholism.- Physical Dependence as a Criterion of Alcoholism.- Tolerance, Physical Dependence, and Craving.- Implications for Prevention and Treatment.- Important Generalizations About Acquired Tolerance and Physical Dependence.- Potential Applications.- Conclusion.- References.- 11 Brain Dysfunction and Alcohol.- Structural Brain Damage.- Incidence of Brain Damage.- The Relationship between Structural Brain Damage and Neuropsychological Tests.- Reversibility of Structural Damage.- Summary.- Evoked Potentials.- Acute Alcoholization.- Chronic Alcohol Abuse.- Concluding Remarks.- References.- 12 Cognitive Deficits in Alcoholics.- Short-term Effects of Alcohol Ingestion.- Memory Deficits in Intoxicated Alcoholics.- Other Cognitive Deficits in Intoxicated Alcoholics.- Long-term Effects of Alcohol Ingestion.- Global Measures of Intellectual Integrity.- Abstract Reasoning.- Perception.- Learning and Memory.- Recovery of Function.- Theoretical Considerations.- Right Hemisphere Hypothesis.- Frontal System Hypothesis.- Accelerated Aging Hypothesis.- Continuity Hypothesis.- Possible Acquired Limitations in Information Processing.- References.- 13 Prenatal Effects of Alcohol Abuse in Humans and Laboratory Animals.- Historical Introduction to Alcohol Abuse in Pregnancy.- Intrauterine Effects of Maternal Alcohol Abuse in Humans.- The Fetal Alcohol Syndrome.- Prevalence of the Fetal Alcohol Syndrome.- The Continuum of Reproductive Deficit Associated with Maternal Alcoholism.- Associated Risk Factors in Intrauterine Alcohol Effects.- Areas for Future Research.- Animal Models of Maternal Alcohol Use and Abuse.- Theoretical Considerations.- Mechanisms.- Alcohol Effects on Offspring.- Maternal Factors.- Paternal Factors.- Areas for Future Research.- The Importance of Fetal Alcohol Syndrome to Problems of Female Alcohol Abuse.- Conclusions.- References.- 14 Amethystic Agents in the Treatment of Alcohol Intoxication.- Available Antagonists of Centrally Active Drugs.- Naloxone.- Other Antagonists.- Putative Alcohol Antagonists.- Substances Which May Alter Nerve Function.- Substances Which Enhance Ethanol Elimination.- Substances Which May Affect Acetaldehyde.- Substances or Conditions with Unknown or Multiple Mechanisms.- Conclusions and Recommendations for Future Study.- References.