Clozapine-induced potentiation of latent inhibition is due to its action in the conditioning stage: implications for the mechanism of action of antipsychotic drugs

Eran Shadach, Joram Feldon, Ina Weiner
1999 International Journal of Neuropsychopharmacology  
Latent inhibition (LI) refers to retarded conditioning to a stimulus as a consequence of its non-reinforced preexposure. LI is impaired in some subsets of schizophrenic patients and in rats treated with amphetamine. Antipsychotic drugs (APDs) potentiate LI under conditions that are insufficient to produce LI in control animals, namely, low number of pre-exposures or high number of conditioning trials. The present experiments tested the proposition that LI potentiation under both conditions
more » ... oth conditions stems from the action of APDs in the conditioning stage. Experiments 1-3 used 10 pre-exposures and 2 conditioning trials, and tested the effects of 2n5, 5, and 10 mg\kg clozapine, respectively. Experiments 4-6 used 40 pre-exposures and 5 conditioning trials, with clozapine doses as above. Clozapine was administered in either the pre-exposure, the conditioning stage, or in both. In all the experiments, vehicle controls did not show LI. Overall, clozapine administration in conditioning, irrespective of drug condition in pre-exposure, produced LI. The implications of these results for the mechanism of action of antipsychotic drugs are discussed.
doi:10.1017/s1461145799001583 pmid:11285144 fatcat:jzqprh6yrzgqjllt5dbwx4ouia