The majority of people who drink alcohol drink moderate amounts without serious consequences, but for a subset of individuals, drinking becomes excessive, leading to serious medical, social and legal consequences. The medical consequences alone may reduce expected life span by as much as 20 years; the social and legal consequences, including accidents, conflict with family and friends, job loss and arrest, severely decrease the quality of that shortened life. Recently, it has been recognized that individual differences in liability for alcohol abuse and alcoholism are associated with inherited personality traits. In particular, two patterns have been identified, 1) the disinhibited personality in which alcoholism accompanies high novelty-seeking, risk-taking, and indifference to social rewards and 2) the anxious personality, in which alcohol serves to reduce anxiety. In the present proposal, rats genetically selected for high or low levels of voluntary consumption of alcohol will be tested in models of disinhibition and anxiety to identify the precise neurobiological mechanisms that link each of these behaviors with alcohol drinking. Project 1 combines behavioral and physiological measures to assess the relationship between responses to novelty, attention, anxiety and anticipation to alcohol drinking. In project 2, behavioral and neurobiological techniques are combined to assess differences in brain arousal and inhibitory systems in the genetically selected lines. Project 3 explores the role of the mesocorticolimbic dopamine system in responses to novelty and alcohol drinking. By developing a better understanding of the inherited influences alcohol drinking, the basic biological mechanisms that increase individual liability for alcoholism can be better understood, and targeted strategies for prevention and treatment developed.
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