Comparison of susceptibilities to the effects of antipsychotic drugs on lever-press avoidance responses between mice and rats

Abstract

Effects of antipsychotic drugs, chlorpromazine, haloperidol and tetrabenazine, on lever-press avoidance responses under Sidman avoidance (response-shock interval = 30 sec and shock-shock interval = 5 sec) and discriminated avoidance (intertrial interval = 25 sec and warning duration = 5 sec) situations in male mice of the dd strain were investigated. The results were compared with those in male rats of the Wistar strain. All the drugs tested were administered s.c., and the avoidance responses of the mice and rats were observed for 1 hr after each administration. Chlorpromazine, haloperidol and tetrabenazine suppressed the avoidance responses of the mice and rats in a dose-dependent manner. The susceptibilities of the mice to these drugs were calculated to be 1/5-1/6 as low as those of the rats. However, the potencies of the avoidance-suppressing effects of chlorpromazine, haloperidol and tetrabenazine were estimated to be 1:20:1.3 and 1:18:1.4 by the Sidman avoidance responses in the mice and rats, respectively, and 1:18:1.1 by the discriminated avoidance responses in both the mice and rats. These results suggest that the conditioned lever-press avoidance responses in mice, as well as those in rats, are applicable for the evaluation of antipsychotic drugs.