Grant: Master's Award: Canada Graduate Scholarships

Environmental cues that have been paired with the intake of alcohol can induce craving, which may lead to relapse in recovering alcoholics. How the brain regulates and controls cue-driven alcohol craving remains unknown. The proposed project seeks to investigate the role of a brain structure, the basolateral amygdala (BLA), and a specific neurotransmitter, dopamine, in this effect. These studies will be conducted using a well-established animal model of Pavlovian-conditioned alcohol seeking that will allow the assessment of neural mechanisms that underlie the specific influence of discrete alcohol-predictive cues on behavior. Male rats will be trained in a specific context to discriminate between two 10-sec auditory cues. One cue, referred to as the CS+, is always paired with the delivery of a drop of alcohol into a fluid receptacle, whereas the second cue (the CS-) is not. Behavioral discrimination will be measured by recording head entries into the fluid port during CS presentations. Once rats are consistently making more responses to the CS+ than the CS- they will receive habituation sessions to a new context where the cues and alcohol are withheld. After the rats have learned that the new context is not associated with alcohol cue-driven alcohol seeking will be tested by presenting the CS+ and CS- as before, without alcohol delivery. To determine if functional activity in the BLA is required for cue-driven alcohol seeking, this structure will be temporarily inactivated before the test. To examine the role of dopamine, a dopamine D1-receptor antagonist will be infused into the BLA before the test. Control rats in both studies will receive a saline infusion into the BLA. We predict that BLA inactivation will reduce responding to the alcohol-associated CS+ and that dopamine in the BLA is required for cue-driven alcohol seeking. These results will have important implications for medications aimed at preventing relapse to alcoholism.