In this study, we examined how family history affects the brain’s response to alcohol’s olfactory cues in non-dependent, at-risk heavy drinkers. We also sought to determine how acute alcohol exposure affects the reward system’s response to alcohol’s conditioned cues by using clamped intravenous (IV) alcohol infusion— a method that prescribes a constant level of brain alcohol exposure throughout functional image acquisition, and avoids the highly variable time courses of breath alcohol concentrations that accompany oral consumption (O’Connor et al., 1998; Plawecki et al., 2007; Ramachandi et al., 2004; Ramchandani et al., 1999). We hypothesized that a family history of alcoholism would be associated with stronger responses to alcoholic drink aromas in the mesocorticolimbic reward system, and that a low-level of steady-state brain exposure to alcohol would potentiate these stimulus-induced responses (Bragulat et al., 2008). Such a potentiation could reflect a possible substrate for priming, when alcohol exposure increases desire to drink (De Wit, 1996; De Wit, 2000). We focused our hypotheses on the ventral tegmental area (VTA) and ventral striatum, and on the medial frontal brain regions to which the VTA and ventral striatum directly project (Chiba, Kayahara, & Nakano, 2001; Haber et al., 2006; Williams & Goldman-Rakic, 1998).
