CHANGES IN ANXIETY-LIKE BEHAVIOR FOLLOWING SHORT-TERM VOLUNTARY ALCOHOL DRINKING IN AGING MICE

Aging is a critical but understudied factor influencing ethanol consumption and withdrawal-related behaviors, while anxiety is one of the most prevalent negative affective consequences of alcohol withdrawal. This study evaluated the impact of aging on short-term alcohol withdrawal, focusing on anxiety-like behavior. Male C57BL/6J mice aged 2, 6, and 9 months were subjected to a voluntary chronic intermittent alcohol consumption paradigm (six cycles of drinking in the dark, 6xDID), followed by 24h of withdrawal; age-matched control groups received water. Alcohol intake, blood ethanol concentration (BEC), and anxiety-like behavior were assessed using the open field (OF), novel object (NO), and elevated plus maze (EPM) tests. During 2h drinking sessions, 2- and 6-month-old mice showed comparable ethanol intake (2-months: 2.80±0.28 g/kg; 6-months: 2.86±0.19 g/kg), whereas 9-month-old mice consumed significantly less ethanol (2.03±0.14 g/kg;P<0.03). A progressive increase in ethanol intake across drinking sessions was observed in 2- and 6-month-old mice (P<0.05), but not in 9-month-old mice. Despite similar ethanol intake, 6-month-old mice exhibited higher BECs than 2-month-old mice (178.3±14.0 vs 92.0±19.9 mg/dL;P=0.005). During withdrawal, ethanol-exposed mice displayed increased anxiety-like behavior. 6-month-old ethanol mice spent less time in the OF center than controls (12.2±1.3% vs 20.7±3.4%; P=0.031). However, 9-month-old ethanol mice showed a markedly more anxiogenic phenotype compared to 6-month-old ethanol mice with reduced OF center time (3.47±0.33%) and EPM open-arm time (0.61±0.33%; P<0.0001). These findings indicate that aging exacerbates anxiety-like behavior following short-term alcohol withdrawal, supporting the translational relevance of this voluntary drinking model.