Restoration of latent inhibition by olanzapine but not haloperidol in entorhinal cortex-lesioned rats

Rationale: Latent inhibition (LI) refers to the decrease in conditioned res ponse induced by the repeated non-reinforced pre-exposure to the conditione d stimulus before its pairing with the unconditioned stimulus during the co nditioning stage. LI has been considered as a relevant animal model for the study of the biological bases of schizophrenia. LI has recently been demon strated to depend on the integrity of the entorhinal cortex, as lesioning: of this area disrupted LI. Objectives: The present study aimed to verify wh ether the classical neuroleptic haloperidol and/or the atypical antipsychot ic olanzapine would prevent the effect of entorhinal cortex lesioning. Meth ods: LI was studied in an off-baseline conditioned emotional response (CER) paradigm in which a tone is paired with a footshock. Entorhinal cortex les ions were produced by the electrolytic method. After a recovery period, bot h lesioned and control rats received either haloperidol (0.3 mg/kg), olanza pine (0.3 mg/kg) or vehicle before both the pre-exposure and conditioning s tages of the experiment. Results: In control rats, pre-exposure to the tone induced LI, which was affected by neither haloperidol nor olanzapine. Lesi oning of the entorhinal cortex produced a deficit of LI, which was restored by olanzapine but not by haloperidol. Conclusions: This result suggests a dissociation of the anatomical and pharmacological targets of the two drugs . The possible involvement of dopamine D3 receptors in the effects of olanz apine is discussed.