Acetylcholine Release in the Dorsal Lateral Straitum During Social Approach Task

Nicotine Decreases ACh Release in the DS leading to a Serenic Effect during Social Approach Task Acetylcholine (ACh) regulates attention, learning, and stress responses (Benarroch E. E., 2012). The dorsal striatum (DS), essential for stimulus-response learning, is also linked to anxiety and compulsivity (Casado-Sainz et al., 2021). We used behavioral pharmacology and in vivo fiber photometry to study ACh responses during social approach tasks in the dorsal striatum. Male and female C57BL/6J mice underwent stereotaxic surgeries to inject a fluorescent ACh sensor (ACh.Sn.Fr) and implant fiber optic cannulas in the DS. Using in vivo fiber photometry, we tracked ACh release during the Three Chamber paradigm, where mice explored a novel conspecific vs. a cage mate. Tests included both same-sex and opposite-sex novel mice. We also measured ACh release after systemic nicotine or saline injections and repeated the Three Chamber Test post-administration. Data was analyzed using custom MATLAB scripts, and behavior was assessed manually or via DeepLabCut for time spent near novel vs. cage mate mice. Our results showed that mice spent more time exploring opposite-sex novel mice than same-sex novel mice. We found that DS ACh increased significantly during the exploration of same-sex novel mice compared to the exploration of opposite-sex mice. Second, our results demonstrated that systemic nicotine injections significantly decreased ACh in the DS compared to saline injections. Finally, we found that systemic nicotine injections vs saline increased the time spent with novel same-sex mice only. We did not find a significant change in time spent with opposite-sex novel mice following nicotine or saline injections. Overall, these results suggest that ACh release in the dorsolateral striatum signals social threat/novelty and Nicotine administration can have a serenic effect.