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Excessive alcohol consumption leads to premature deaths and high societal costs, often exacerbated by relapses triggered by alcohol-associated cues. This study employed a mouse model of binge alcohol drinking to investigate if such cues elicit anticipatory behavior. We found that over time, all mice became responsive to cues irrespective of fluid provided. Surprisingly, control males spent more time near their sipper than other groups during cues, despite only ethanol mice exhibiting craving-associated drinking patterns.


Background: Excessive alcohol consumption contributes to approximately 140,000 deaths and $249 billion dollars in societal costs each year. This is due in part to high rates of relapse by those with an Alcohol Use Disorder (AUD), which is often precipitated by intense cravings following exposure to alcohol-associated cues. A significant gap exists in our understanding of the neurobiological underpinnings of alcohol-cue learning and associated behaviors, which if filled may provide avenues for the development of novel therapeutic targets to mitigate cue-induced alcohol craving.

Methods: C57BL/6J mice were provided access to either ethanol or water for 2 hours daily for 15 days using drinking-in-the-dark (DID) paradigm. An additional (control) group received no fluid. Each fluid-assigned group was given fluid access using specialized sippers that provide temporally accurate recordings of drinking volumes. Immediately prior to the experimenter entering the room and providing fluid access, 1 minute of discrete (~100) auditory ‘clicks’ were presented in the testing room using a remote computer interface. Home cage behavior was continuously monitored using overhead IR cameras.

Results: Significant increases in the percent of distance travelled during the cue between the first and last day were observed across all groups, indicating the cue’s salience and potential for sensitization. Additionally, significant sex differences were noted, with females exhibiting higher activity than males. Water-sipper receiving males spent significantly more time in proximity to the sipper compared to the ethanol and control groups during the cue. Clear evidence of increases in motivation for alcohol were observed (i.e. front-loading), but not for water.

Conclusion: Collectively, these data suggest that behavioral responses to fluid access depend on the fluid provided and sex. Furthermore, they suggest that increases in motivation for alcohol may involve conservation of energy resources until the precise time of access to potentially maximize drinking efficiency.



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