Antagonism of amphetamine-induced disruption of latent inhibition by the atypical antipsychotic olanzapine in rats

The present study aimed at characterising the effects of the new antipsychotic olanzapine in a Latent Inhibition (LI) paradigm. A conditioned emotional response (CER) procedure was used, consisting of three stages: pre-exposure, in which the to-be-conditioned stimulus (a tone) was presented six times without being followed by reinforcement; conditioning, in which the pre-exposed stimulus was paired twice with reinforcement (a foot shock); and test, in which LI was assessed by the suppression of licking during the tone presentation. In Experiment I, it was found that pre-treatment with an intermediate dose (0.312mg/kg) of olanzapine, but not with lower (0.003; 0.031mg/kg) or higher doses (0.625; 1.25mg/kg), restored LI in amphetamine-treated (1.5mg/kg) animals. This effect could not be attributed to a disruptive effect of olanzapine on CER learning, as olanzapine per se had no effect on this conditioning (Experiment 2). In Experiment 3, olanzapine did not antagonise the amphetamine-induced locomotor hyperactivity. As olanzapine has not only dopaminergic, but also serotonergic, adrenergic, histaminergic and cholinergic activities, the differential effects of olanzapine on amphetamine-induced disruption of LI and hyperactivity may reflect an action on several pharmacological targets, possibly interacting with one another.