Low dose ethanol effects on reward learning and motivation

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Project Summary More than half of frequent alcohol drinkers in the United States do so at a level that does not meet diagnostic criteria for an alcohol use disorder. This chronic alcohol drinking, even at sub-diagnostic levels, can still produce profound impacts on neurobiology and behavior. Clinical studies have shown that low levels of acute ethanol drinking within an hour after learning can enhance task consolidation and memory recall. In contrast, drinking before learning attenuates memory recall. Despite the prevalence of frequent, low-dose ethanol consumption, the effects of repeated post-training ethanol on learning and the neurobiological consequences of this level and frequency of exposure remain largely unknown. Furthermore, it is unclear whether these effects are a result of ethanol exposure during the period of protein synthesis-dependent memory consolidation specifically or, rather, a general outcome of post-training ethanol exposure. Our preliminary data suggest that chronic, low-dose ethanol exposure after behavioral training increases sucrose reward-seeking behavior, while only ethanol exposure specifically during protein synthesis-dependent consolidation enhances sucrose reward motivation. The ventral hippocampus (vHPC) is a key structure for memory consolidation and reconsolidation. It is further particularly sensitive to ethanol-induced disruptions, making it a likely contributor to ethanol exposure effects on reward learning. This may be mediated by vHPC projections to the nucleus accumbens shell (NAcS) as this circuit is critical in tracking reward value and reward-related contexts. Thus, this proposal will test the overarching hypothesis that chronic, low-dose ethanol exposure after behavioral training impacts reward seeking and motivation and modulates vHPC → NAcS circuit engagement. Aim 1 will combine GCaMP6 photometry with behavioral assessment in order to test the hypothesis that chronic, low-dose ethanol exposure enhances reward seeking and motivation, which are accompanied by alterations in vHPC → NAcS activity. Aim 2 will use chemogenetic strategies to test the hypothesis that inhibiting vHPC → NAcS activity during reward learning can attenuate escalations in reward-seeking behavior and motivation independent of ethanol impacts on this circuit. The results from these experiments will expand our understanding of the impacts of long-term low dose ethanol exposure on behavior and neurobiology, which is an area that remains severely understudied in the alcohol use field. Further, this fellowship will enable the applicant to build on her expertise in neural circuit regulation of alcohol use by integrating a conceptual understanding of low-dose ethanol effects on behavior and technical training in in vivo calcium imaging in neurons. The abundance of resources and opportunities available in the Barker lab and at Drexel University will ensure that the applicant is prepared and qualified for a long-term career in science.