Voluntary binge‐patterned alcohol drinking and sex‐specific influences on monoamine‐related neurochemical signatures in the mouse gut and brain

Background Altered monoamine (i.e., serotonin, dopamine, and norepinephrine) activity following episodes of alcohol abuse plays key roles not only in the motivation to ingest ethanol, but also physiological dysfunction related to its misuse. Although monoamine activity is essential for physiological processes that require coordinated communication across the gut–brain axis (GBA), relatively little is known about how alcohol misuse may affect monoamine levels across the GBA. Therefore, we evaluated monoamine activity across the mouse gut and brain following episodes of binge‐patterned ethanol drinking. Methods Monoamine and select metabolite neurochemical concentrations were analyzed by ultra‐high‐performance liquid chromatography in gut and brain regions of female and male C57BL/6J mice following “Drinking in the Dark” (DID), a binge‐patterned ethanol ingestion paradigm. Results First, we found that alcohol access had an overall small effect on gut monoamine‐related neurochemical concentrations, primarily influencing dopamine activity. Second, neurochemical patterns between the small intestine and the striatum were correlated, adding to recent evidence of modulatory activity between these areas. Third, although alcohol access robustly influenced activity in brain areas in the mesolimbic dopamine system, binge exposure also influenced monoaminergic activity in the hypothalamic region. Finally, sex differences were observed in the concentrations of neurochemicals within the gut, which was particularly pronounced in the small intestine. Conclusion Together, these data provide insights into the influence of alcohol abuse and biological sex on monoamine‐related neurochemical changes across the GBA, which could have important implications for GBA function and dysfunction. We examined monoamine neurochemicals in brain and gut regions following voluntary binge‐like alcohol drinking in male and female mice. Binge‐like drinking robustly influenced striatum and hypothalamic monoamines, while having an overall mild effect on gut neurochemicals. However, neurochemical patterns between the small intestine and striatum were correlated, adding to evidence of modulatory activity between these areas. Together, the sex‐specific and alcohol‐related monoaminergic influences observed in this study could have key implications for gut‐brain axis function and dysfunction.