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

Department of Therapeutics and Pharmacology The Queen's University of Belfast, Belfast

Robert Bell

School of Psychology The Queen's University of Belfast, Belfast

David J. King

1Department of Therapeutics and Pharmacology The Queen's University of Belfast, Belfast

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.

Key Words: amphetamine • atypical antipsychotic • clozapine • haloperidol • latent inhibition • rat

Journal of Psychopharmacology, Vol. 12, No. 2, 215-219 (1998)
DOI: 10.1177/026988119801200213


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