Disruption of prepulse inhibition of startle reflex in a neurodevelopmental model of schizophrenia: reversal by clozapine, olanzapine and risperidone but not by haloperidol.
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.
Le Pen
Gwenaëlle
G
Pharma Division, Preclinical CNS Research, F-Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland.
Moreau
Jean-Luc
JL
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001569:Benzodiazepines; D003024:Clozapine / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D006220:Haloperidol / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D012110:Reserpine / Q000494:pharmacology* / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D012110:Reserpine; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine