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 antip sychotic olanzapine in a Latent Inhibition (LI) paradigm. A conditione d emotional response (CER) procedure was used, consisting of three sta ges: pre-exposure, in which the to-be-conditioned stimulus (a tone) wa s presented six times without being followed by reinforcement; conditi oning, in which the pre-exposed stimulus was paired twice with reinfor cement (a foot shock); and test, in which LI was assessed by the suppr ession of licking during the tone presentation, In Experiment 1, it wa s found that pre-treatment with an intermediate dose (0.312 mg/kg) of olanzapine, but not with lower (0.003; 0.031 mg/kg) or higher doses (0 .625; 1.25 mg/kg), restored LI in amphetamine-treated (1.5 mg/kg) anim als, This effect could not be attributed to a disruptive effect of ola nzapine on CER learning, as olanzapine per se had no effect on this co nditioning (Experiment 2), In Experiment 3, olanzapine did not antagon ise the amphetamine-induced locomotor hyperactivity, As olanzapine has not only dopaminergic, but also serotonergic, adrenergic, histaminerg ic 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 wit h one another.