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 re sponding after diazepam (10 mg/kg, PO). In a separate group of drug-na ive mice, diazepam (1-30 mg/kg, PO) produced a robust antipunishment e ffect under identical experimental conditions, but crossover to buspir one (10 mg/kg, PO) failed to enhance punished responding. In a further experiment using this conflict model, two groups of benzodiazepine-ex perienced 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 diaze pam (5 mg/kg) daily for four weeks followed by a test with diazepam; b oth groups exhibited a clear antipunishment effect. Finally, a group o f benzodiazepine-experienced mice given vehicle daily for four weeks f ollowed by a test with vehicle failed to exhibit an antipunishment eff ect. 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.