Acute and chronic administration of buspirone fails to yield anxiolytic-like effects in a mouse operant punishment paradigm.

Drug-naive mice failed to exhibit antipunishment effects of ascending doses of buspirone (1-30 mg/kg, PO) in an operant punishment paradigm; however, these same mice subsequently exhibited increased punished responding after diazepam (10 mg/kg, PO). In a separate group of drug-naive mice, diazepam (1-30 mg/kg, PO)produced a robust antipunishment effect under identical experimental conditions, but crossover to buspirone (10 mg/kg, PO) failed to enhance punished responding. In a further experiment using this conflict model, two groups of benzodiazepine-experienced mice received daily oral administration of either vehicle or buspirone (5 mg/kg) for four weeks followed by a test with buspirone; neither group exhibited an antipunishment effect. Two other groups of benzodiazepine-experienced mice received either oral vehicle or diazepam (5 mg/kg) daily for four weeks followed by a test with diazepam; both groups exhibited a clear antipunishment effect. Finally, a group of benzodiazepine-experienced mice given vehicle daily for four weeks followed by a test with vehicle failed to exhibit an antipunishment effect. Thus, despite the attempt to optimize some important experimental conditions in this mouse conflict paradigm, buspirone still failed to produce an antipunishment effect. In contrast, diazepam consistently exhibited a robust anxiolytic-like effect under the same experimental conditions.