Our long-term goal is to develop a better understanding of predisposing motivational characteristics of persons at risk for alcoholism. Alcohol addiction is a behavioral disorder with genetic and environmental contributions. Increased risk for alcoholism in persons with a positive family history is an expression of more basic inherited traits. These traits are thought to derive from altered activity of brain regions regulating emotional experience and expression. The present project will examine persons with a family history of alcoholism and classify them according to their cortisol response to naltrexone, an opiate receptor blocker. The magnitude of cortisol response to naltrexone is a useful indicator of an abnormally elevated central opioid regulation. This elevation in opioid function is also an indicator of differential functioning of other brain regulatory systems. These systems have an impact on functioning of the limbic system and prefrontal cortex, and in turn may provide insights into underlying alterations in motivation-related behavior in persons who are at high risk for alcoholism. We plan to test 200 healthy volunteers, 100 with a family history of alcoholism, 100 without. We predict that elevated central opioid activation in high-risk individuals will be observable in four domains of function: 1) Behavioral undercontrol: the person's temperamental balance of positive to negative affect should be less stable and weighted toward dysphoria. 2) Cognitive processing will be impaired on tests or working memory. 3) Choice behaviors will show biases toward risk-taking and impulsivity under motivational conditions. Tests of behavioral economics (delay-discounting) will show a short time horizon. 4) Visceral responses to psychological stress will be blunted, with reduced responses in the stress hormone, cortisol, and autonomic measures controlling the heart. Our longer-term goal is to perform annual follow-ups of subjects who have taken part in the study to seek factors that determine long-term drinking patterns. This project seeks to understand psychological and behavioral characteristics of young adults who are children of alcoholics to identify those personal characteristics that put them at high risk for future alcoholism. Prevention of complex disorders such as alcoholism requires early identification of those persons who are most at risk, and this project seeks to provide new information about such risk. ? ? ?
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