Delineating sex-specific abstinence-induced negative affective behavior in insular circuitry

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Project Summary/Abstract Alcohol Use Disorder (AUD) is a growing problem in our nation and worldwide. The COVID-19 pandemic has led to a significant increase in alcohol use, with a particularly sharp rise in women, with many people relapsing due to the negative affective states correlated with abstinence. A functional connectivity network of abstinence-induced negative affect is needed to fully understand these states in order to better help people suffering with AUD. Previous work in our lab has elucidated parts of the pathway, delineating an insula to BNST pathway that is activated during alcohol abstinence induced negative affect by testing male and female though locomotor based behavioral assays. Due to findings in recent literature, however, it is possible that these locomotor-based assays do not reveal the full scope of negative affective behavior in female mice. The applicant, Amanda Salazar, proposes to build on the experiments in the parent grant to test a non-locomotor based behavioral assay that has not been tested in our CDFA model, and is therefore a logical extension of the parent grant. This will allow us to properly identify sex differences in negative affect in mice during alcohol abstinence. We hypothesize that female mice will exhibit a much stronger alcohol abstinence-induced negative affect-like phenotype in startle response tests (acoustic, air puff, foot shock) compared to male mice. Amanda will build off her molecular biology background to gain meaningful training in alcohol models, stereotaxic surgery, fiber photometry, and statistical analysis and presentation of data. Mentorship will also focus on furthering scientific communication skills and engaging in outreach within the lab, the program, and the community to reach her goal of admittance into a PhD program