Glucose and fructose differently mediate alcohol cocktail drinking in female and male rats: interaction of glucose and alcohol on post-ingestive behavior

Kuebler, I. R. K.; Zimmerman, G.; Ng, S. Q.; Schneider, H. M.; Sextro, K.; Denning, A.; Mattes, B.; Matuszeski, M.; Suarez, M.; Wakabayashi, K. T.

doi:10.64898/2026.04.15.718765

bioRxiv · 10.64898/2026.04.15.718765

Glucose and fructose differently mediate alcohol cocktail drinking in female and male rats: interaction of glucose and alcohol on post-ingestive behavior

Kuebler, I. R. K.·Zimmerman, G.·Ng, S. Q.·Schneider, H. M.·Sextro, K.·Denning, A.·Mattes, B.·Matuszeski, M.·Suarez, M.·Wakabayashi, K. T.

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Abstract

Sweetened alcoholic beverages are thought to contribute to developing Alcohol Use Disorder by increasing palatability. One monosaccharide, glucose, readily enters the brain more than fructose and directly impacts the activity of central neurons. The objective of this study is to determine the impact of glucose versus fructose on alcohol drinking patterns in female and male rats. Rats drank alcohol cocktails (1.25%-10%) containing either glucose or fructose (10%) in 4-hour sessions. We sought to parse orosensory effects from post-ingestive central effects by analyzing drinking microstructure. We compared measures of palatability and post-ingestive feedback between early and later in the session when brain levels of alcohol and glucose are different. We found that rats of both sexes drank more low alcohol glucose cocktails than cocktails containing fructose by volume and by overall calories. When considering the dose of alcohol, glucose potentiated alcohol intake by shifting the dose-response curve leftward compared to similar fructose cocktails. We found that drinking patterns associated with palatability remained stable for both types of cocktails over the entire drinking session. In contrast, post-ingestive behavior related to brain mediated satiety or positive feedback showed a greater influence of the session time, as well as a greater interaction with sex. Overall, our results suggest that glucose and alcohol interact to impact central regulation of cocktail drinking. This highlights that the type of sugar within cocktails interacts and ultimately have different effects on brain regulated alcohol drinking.

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Kuebler, I. R. K., Zimmerman, G., Ng, S. Q., Schneider, H. M., Sextro, K., Denning, A., Mattes, B., Matuszeski, M., Suarez, M., Wakabayashi, K. T.. 2026-04-20. Glucose and fructose differently mediate alcohol cocktail drinking in female and male rats: interaction of glucose and alcohol on post-ingestive behavior. https://doi.org/10.64898/2026.04.15.718765

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