A lever-release version of the conditioned avoidance response paradigm: Effects of haloperidol, clozapine, sulpiride, and BMY-14802

Abstract

Rats trained on a lever-release version of the conditioned avoidance response (CAR) task were used to test the behavioral effects of established and putative antipsychotic drugs. Baseline CAR latencies decreased as the conditioned-unconditioned stimulus interval was shortend from 500 to 250 ms. Haloperidol, clozapine, and BMY-14802 decreased successful avoidance responses and increased avoidance latencies in a dose-dependent manner without affecting the latency of escape responses. In contrast, sulpiride failed to affect either successful avoidance response rates or avoidance latency. Sulpiride, however, significantly attenuated d-amphetamine-induced locomotion and rearing compared to vehicle-treated controls. Similar effects of these antipsychotics have been reported on shuttlebox avoidance, and these results now are confirmed in a CAR paradigm that achieves greater control over behavior. Because this paradigm elicits a discrete forelimb response without activating numerous muscle groups, it is potentially useful as a tool for examining neuronal mechanisms underlying the behavioral effects of antipsychotic drugs.