Altered Interoception of an Intoxicated State after Administration of Semaglutide (2024)

Undergraduate: McKinley Windram

Faculty Advisor: Joyce Besheer
Department: Bowles Center for Alcohol Studies, Psychiatry

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Recent studies provide promising data supporting semaglutide as a potential treatment for alcohol use disorder (AUD). Semaglutide is commonly prescribed for obesity, and some patients have reported changes in their perception of the interoceptive effects of alcohol as well as reduced drinking frequency. To test whether semaglutide modulates the interoceptive effects of alcohol, we used an operant discrimination procedure to train rats to discriminate the interoceptive effects of alcohol from water. We tested the effects of semaglutide over time at two different doses (0.03 mg/kg and 0.01 mg/kg) via an every-other-day injection regimen across 15 days, with tests occurring on days 1, 5, 15, as well as afterwards on days 17 and 18. With acute administration alcohol-appropriate responding was reduced at all doses. At the 0.03 mg/kg dose, the response rate was initially lower during the acute test but did not differ from controls during the next test day. When semaglutide administration was stopped, alcohol-appropriate responding returned to baseline. A second acute test was conducted to evaluate two lower doses (0.01 mg/kg and 0.003 mg/kg) in the hopes of finding an effective dose that did not alter response rate. The 0.003 mg/kg dose had no effect, but the 0.01 mg/kg dose altered interoception without affecting response rate and thus may serve as a potential therapeutic dose. This study demonstrated that semaglutide disrupted alcohol interoception. This may explain how semaglutide reduces alcohol consumption in preclinical models and could be an important part of semaglutide’s therapeutic potential for treating AUD.