Enhancement of latent inhibition in the rat at a high dose of clozapine.

The present experiments investigated clozapine (2.5, 5 and 10 mg/kg) and haloperidol (0.1 mg/kg) administration on latent inhibition (LI) in rats. Clozapine's ability to antagonize amphetamine-induced disruption of LI was also assessed. A conditioned emotional response procedure was employed. In the pre-exposure stage, 'pre-exposed' rats received 10 (Experiment 1) or 40 (Experiment 2) presentations of a flashing light stimulus without reinforcement. During the conditioning phase, the light stimulus was paired with a footshock. At test, LI was expressed by the extent of suppression of water licking during flashing light presentation. Both clozapine (10 mg/kg) and haloperidol (0.1 mg/kg) significantly facilitated LI. In addition, clozapine significantly reversed the disruption of LI induced by amphetamine (1.0 mg/kg). These results with clozapine illustrate that LI is sensitive to antipsychotics which differ in their mode of action and furthermore emphasize the value of LI as a test model for detecting the antipsychotic potential of novel drugs.