FMRI OF THE MESOLIMBIC DOPAMINE SYSTEM IN RISKY DRINKERS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The investigator's long term goal is to use functional imaging to study mesolimbic dopamine vulnerabilities that lead to alcoholism and treatment relapse. This knowledge is essential for understanding disease mechanisms and developing drug treatments. The aims of this GCRC application are to 1) gain preliminary data to support an R01 application to NIAAA and 2) eventually support a funded NIAAA that uses fMRI and alcohol olfactory cues to study the ventral tegmental area and nucleus accumbens in individuals at differential risk for alcoholism. The overall aims of the larger study will be to 1) identify olfactory cue-elicited differences in cerebral systems that differentiate between subjects at high- and low- risk for developing alcoholism, and 2) find subjective responses to alcohol cues that predict mesolimbic dopamine area signals. To do this, we will use fMRI to image mesolimbic dopamine area responses to alcoholic odor cues to replicate and extend our preliminary findings into larger groups of high-risk subjects (heavy drinkers with a family history of alcoholism) and low risk controls. We will do so with a low dose alcohol primary and during placebo control. We will also study changes in desire to drink 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 experimental animal findings into the key population of interest - human subjects with problem drinking.