Alcohol is far more frequently associated with violent and aggressive behavior than all other drugs combined. The proposed research addresses our need to better understand the basic behavioral and neurobiological mechanisms of the alcohol-aggression link. Based on the discovery in the previous funding period that it is possible in several animal models to identify those individuals that are most prone to the aggression- heightening effects, the current proposal aims to delineate the behavioral, physiological and neurochemical characteristics of this subgroup of individuals. The marked individual differences in the aggression-heightening effects of alcohol and in the self-administration pattern for alcohol prompt focus on individual behavioral and physiological characteristics. Detailed investigations of GABA/A receptors using both pharmacological and endocrinological manipulations will examine this critical site of alcohol action in the modulation of aggressive behavior and related emotional expressions. Six series of experiments are proposed, the first focusing on the reciprocal relationship between aggression, social stress and alcohol self- administration, the second on a quantitative ethological analysis of the disruption of communicative social signals by alcohol and their neural modulation at GABA/A receptors, the third and fourth on the pharmacological and endocrinological influences on the benzodiazepine/GABA/A receptor complex for attenuating the aggression- heightening effects of alcohol, and the fifth and sixth on the behavioral, physiological and neurochemical characteristics of those individuals who are most prone to show aggression-heightening effects of alcohol. (1) Quantitative analysis of circadian rhythmicity of telemetered blood pressure, heart rate and core temperature, (2) autonomic response and adaptation to environmental, social and pharmacological challenges and (3) functional properties of GABA/A receptor populations are investigated for their predictive values to identify individuals with high propensity to become very aggressive after alcohol.
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