S.19.02 Mechanisms of dopaminergic dysfunction in rats with neonatal ventral hippocampus lesions

Abstract

Neonatal ventral hippocampal (NVH) lesions in rats have been shown to induce behavioral abnormalities at adulthood thought to simulate some aspects of positive, negative and cognitive deficits classically observed in schizophrenic patients. Such lesions induced a post-pubertal emergence of prepulse inhibition deficits reminiscent of the sensorimotor gating deficits observed in a large majority of schizophrenic patients. Here we have investigated the capacity of typical and atypical antipsychotics to reverse PPI deficits seen in NVH-lesioned rats.We show that three atypical antipsychotics (clozapine, olanzapine and risperidone) were able to reverse lesion-induced PPI deficits, in contrast to haloperidol, a classical neuroleptic.These results show that the NVH lesion model seems to be endowed with a fair predictive validity as, like in schizophrenic patients, PPI deficits in lesioned animals were reversed by atypical antipsychotics but not by the typical neuroleptic haloperidol.