Effects of benzodiazepine agonists on punished responding in pigeons and their relationship with clinical doses in humans

Anxiolytic drugs generally produce anticonflict effects in both pigeons and rats, although relatively few anxiolytics have been examined in the pigeon and the procedure has not been as completely validated as the rat model. I n this study, we examined the antipunishment effects of a variety of benzod iazepine agonists in pigeons and compared the relationship between their po tencies to engender anxiolytic-like effects and their clinical doses in hum ans. In pigeons whose responding was maintained under a multiple FR30(food) :FR30(food+shock) schedule. the ben zodiazepine agonists diazepam, flunitra zepam. alprazolam, chlordiazepoxide, lorazepam, flurazepam, bromazepam, med azepam, and clorazepate produced dose-related increases in punished respond ing, and, with the exception of medazepam, decreased unpunished responding at higher doses. Potencies calculated from the percentage of pigeons showin g significant increases in punished responding ranged from 0.081 to 11 m/kg and these potencies were invariably lower than those for decreases in unpu nished responding by factors ranging from 2.2 to more than 14. The comparis on of relative potencies of benzodiazepine receptor agonists in pigeons and humans revealed a high positive correlation (0.90, P<0.005), thus demonstr ating the predictive validity of this preclinical animal model for anxiolyt ic benzodiazepines. The results agree with previous findings of robust anti conflict effects of benzodiazepine receptor agonists and extend further the pharmacological characterization to compounds that have not been examined previously in pigeons.