Effects of clozapine on latent inhibition in the rat

Abstract

In the present study we have examined the effect of clozapine, an atypical antipsychotic drug, on latent inhibition (LI) using the conditioned emotional response (CER) procedure. In this procedure, ten pre-exposures to the to-be-conditioned stimulus result in weak or no LI whereas 30 pre-exposures produce robust LI. Three different experimental protocols were used to study the effects of clozapine: facilitation of LI in animals subjected to ten pre-exposures to the to-be-conditioned stimulus; antagonism of the disruptive effect of amphetamine (1mg/kg, s.c.) on LI in animals receiving 30 pre-exposures; antagonism of the disruptive effect of nicotine (0.6mg/kg, s.c.) on LI in animals receiving 30 pre-exposures. High doses of clozapine (3 and 10mg/kg, s.c.) disrupted the CER in non pre-exposed animals. Despite this, clozapine significantly facilitated the development of LI at 1 and 10mg/kg and significantly attenuated the disruptive effects of nicotine at 0.3 and 1mg/kg and of amphetamine at 2 and 5mg/kg. These results demonstrate that clozapine is active in the LI model and further support the utility of this model in the study of mechanisms of action of antipsychotic drugs.