Anxiogenic behavior in rats during acute and protracted ethanol withdrawal: reversal by buspirone

This study investigated the effectiveness of buspirone in reversing the anxiogenic behaviors occurring during ethanol withdrawal as measured in the elevated plus-maze. In response to anxiogenic drugs, rats spend less time in and make fewer entries onto the open arms of an elevated plus-maze, whereas anxiolytic drugs produce opposite effects. In this study, rats were fed a liquid diet containing 4.5% ethanol for 7 days. Twelve h (acute withdrawal) and 7 days (protracted withdrawal) following cessation of the ethanol diet, rats were tested on the elevated plus-maze. During these withdrawal periods, the percent open-arm entries and time spent on the open arms were significantly reduced relative to animals fed an ethanol-free diet, suggestive of anxiogenic-like symptoms. Buspirone (0.32-1.25 mg/kg) dose dependently reversed the withdrawal-induced decreases in open-arm activity. The anxiolytic-like activity of buspirone observed during ethanol withdrawal may be due to a reduction in serotonergic neurotransmission through activation of presynaptic 5-HT1A autoreceptors. The results obtained in this study suggest that pharmacotherapy with selective 5-HT1A agonists may be beneficial in alleviation of anxiety during ethanol withdrawal.