Buspirone, gepirone and ipsapirone disrupt both active and passive avoidance responding in rats

The anxiolytic drug buspirone and its structural analogues gepirone and ipsapirone produce behavioural effects which differ from those seen with benzodiazepines and barbiturates. Buspirone has been reported to disrupt active avoidance responding without interfering with the ability to escape the aversive stimuli, an effect usually associated with antipsychotic drugs. In the present study, buspirone, gepirone and ipsapirone produced dose-related decreases in one-way, active avoidance responding of rats. However, these drugs did not consistently give rise to a within-session decline in avoidance responding as was seen with the dopamine antagonist metoclopramide. In a second experiment, buspirone, gepirone and ipsapirone disrupted the performance of a passive avoidance response. Rats previously conditioned to remain on a raised platform to avoid shock stepped off the platform after injection of these drugs. A similar effect on the passive avoidance response was not produced by chlordiazepoxide; diazepam, CL 218, 872, haloperidol, imipramine or d-amphetamine. These disruptions of the performance of both active and passive avoidance indicate a unique pharmacological profile for buspirone and similar drugs.