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.
Department of Therapeutics and Pharmacology, The Queen's University of Belfast, UK.
K M
KM
Trimble
R
R
Bell
D J
DJ
King
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001245:Association Learning / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006220:Haloperidol / Q000494:pharmacology; D007266:Inhibition, Psychological; D051381:Rats; D017207:Rats, Sprague-Dawley
D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol