Comparison of the Effects of Clozapine, Risperidone, and Olanzapine on Ketamine-Induced Alterations in Regional Brain Metabolism

摘要: The ability of subanesthetic doses N-methyl-D-aspartate (NMDA) antagonists to induce positive, negative, and cognitive schizophrenia-like symptoms suggests that reduced NMDA receptor function may contribute the pathophysiology schizophrenia. An increasing body evidence indicates antipsychotic drugs, especially those with "atypical" properties, can antagonize effects in a variety experimental paradigms. We demonstrated previously clozapine, prototype atypical antipsychotics, but not haloperidol, typical antipsychotic, blocked ketamine-induced alterations brain metabolism. In this study, clozapine were compared two newer risperidone olanzapine, on regional [(14)C]2-deoxyglucose (2-DG) uptake. A dose ketamine (25 mg/kg) induced robust increases 2-DG uptake limbic cortical regions, hippocampal formation, nucleus accumbens, basolateral amygdala. Pretreatment rats (0.3 before administration did alter ketamine. These data suggest novel pharmacological properties model, addition well characterized actions at D(2) 5HT(2A) receptors. contrast results risperidone, olanzapine However, higher (10 was required completely block than would be expected if 5HT(2) blocking drug solely responsible for its action. challenge paradigm useful model identify drugs characteristics explore mechanisms