EFFECTS OF CLOZAPINE ON LATENT INHIBITION IN THE RAT

In the present study we have examined the effect of clozapine, an atyp ical antipsychotic drug, on latent inhibition (LI) using the condition ed emotional response (CER) procedure. In this procedure, ten pre-expo sures to the to-be-conditioned stimulus result in weak or no LI wherea s 30 pre-exposures produce robust LI. Three different experimental pro tocols were used to study the effects of clozapine: facilitation of LI in animals subjected to ten pre-exposures to the to-be-conditioned st imulus; antagonism of the disruptive effect of amphetamine (1 mg/kg, s .c.) on LI in animals receiving 30 pre-exposures; antagonism of the di sruptive effect of nicotine (0.6 mg/kg, s.c.) on LI in animals receivi ng 30 pre-exposures. High doses of clozapine (3 and 10 mg/kg, s.c.) di srupted the CER in non pre-exposed animals. Despite this, clozapine si gnificantly facilitated the development of LI at 1 and 10 mg/kg and si gnificantly attenuated the disruptive effects of nicotine at 0.3 and 1 mg/kg and of amphetamine at 2 and 5 mg/kg. These results demonstrate that clozapine is active in the LI model and further support the utili ty of this model in the study of mechanisms of action of antipsychotic drugs.