Clozapine, but not haloperidol, prevents the functional hyperactivity of N-methyl-D-aspartate receptors in rat cortical neurons induced by subchronic administration of phencyclidine.

摘要: Repeated exposure of rats to the psychotomimetic drug phencyclidine (PCP) markedly increased response prefrontal cortical neurons glutamate agonist N -methyl-d-aspartate (NMDA) relative α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid. Moreover, acute challenge by PCP produced a significantly reduced block NMDA-induced current. In addition, subchronic administration paired-pulse facilitation, accompanied significant increase excitatory postsynaptic current variance. These results suggest that repeated evoked release amino acids. The enhanced acids NMDA could explain, at least partly, hypersensitive and blockade responses in exposed repeatedly PCP. Pretreatment with atypical antipsychotic clozapine, but not typical haloperidol, attenuates PCP-induced effect. Our support hypothesis clozapine may facilitate receptor-mediated neurotransmission improve schizophrenic-negative symptoms cognitive dysfunction. This novel approach is useful for evaluating cellular mechanisms action drugs.