Enhancement of Latent Inhibition in the Rat by the Atypical Antipsychotic Agent Remoxipride

Abstract

Latent inhibition (LI) is a behavioural paradigm in which repeated nonreinforced preexposure to a stimulus inhibits the formation of subsequent associations to that stimulus. LI is believed to reflect learning to ignore irrelevant stimuli. Disrupted LI has been suggested as an animal model for the attentional deficits observed in schizophrenia. Remoxipride, a selective dopamine D 2 antagonist, is an effective antipsychotic with an atypical clinical profile. We investigated the effects of remoxipride (1.0, 5.0, and 10.0 mg/kg) and haloperidol (0.1 mg/kg) administration on LI in rats. A three-stage conditioned emotional response procedure was employed: a) preexposure: preexposed rats received 10 presentations of a flashing light stimulus without reinforcement, and nonpreexposed rats received no exposure; b) conditioning: the preexposed stimulus was paired with a foot shock over a number of trials; c) test: LI was expressed by the extent of suppression of water licking during flashing light presentation. Animals receiving 0.1 mg/kg of haloperidol or 1.0 or 5.0 mg/kg (but not 10.0 mg/kg) of remoxipride treated the preexposed stimulus as irrelevant after a low number of preexposures. These results illustrate that the LI model is equally sensitive to typical and atypical antipsychotics and reemphasises its utility as a test model for detecting the antipsychotic potential of novel drugs.