fMRI of the mesolimbic dopamine system in risky drinkers

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DESCRIPTION (provided by applicant): The principal investigator's long term goal is to use functional imaging to study limbic system vulnerabilities that lead to alcoholism and treatment relapse. This knowledge is essential for understanding disease mechanisms and developing drug treatments. The objective of this application is to use fMRI and alcohol-related olfactory cues to study the ventral tegmental area, nucleus accumbens, limbic gustatory and orbitofrontal cortex in individuals at differential risk for alcoholism. Aim 1: Determine the effects of family history and recent drinking on olfactory cue-induced responses in mesolimbic dopamine and gustatory areas. We will use fMRI to study gustatory and mesolimbic dopamine area responses to alcoholic odor cues in non-dependent, healthy, social drinkers who vary by family history of alcoholism and recent drinking. Aim 2: Study the effects of low-dose alcohol on cue-induced responses in mesolimbic dopamine, gustatory, and orbital areas. We will study group differences in olfactory cue-elicited signals in these limbic brain areas during steady-state, intravenous alcohol infusion. Aim 3: Examine cue-induced signals in mesolimbic dopamine and gustatory areas as a function of cue-induced craving. We will study changes in desire to drink and salivation following exposure to alcohol cues, and relate those changes to observed signal changes in fMRI. The significance of this research is that it directly extends findings from experimental animal research to the key population of interest- human subjects at risk for developing alcoholism. The work will advance our understanding of how brain function in key regions is associated with one or both of two main risk factors for alcoholism.