The mechanism for the effects of atypical antipsychotics on the cognitive dysfunction of schizophreniavia the modulation of the function of the neuronal network

阐明精神分裂症认知功能障碍的发病机制和治疗机制非常重要，因为这种功能障碍会导致精神分裂症患者严重的社会功能障碍。苯环利定引起的前额叶皮质谷氨酸水平升高和多动障碍可被非典型抗精神病药物多沙平阻断。损毁将谷氨酸能神经元终末投射到前额叶皮质的背侧丘脑，增强了NMDA受体拮抗剂MK-801的行为和神经化学变化。另一种非典型抗精神病药奥氮平可增加前额叶皮质多巴胺D_1受体的蛋白水平，增强大鼠的工作记忆。因此，非典型抗精神病药可增强前额叶皮质N-甲基-D-天冬氨酸受体和多巴胺D_1受体的功能，有可能改善精神分裂症的认知功能障碍。

Clarifying the pathogenesis and the mechanism for the treatment of cognitive dysfunction of schizophrenia is important, because this dysfunction induces serious social dysfunction in patients with schizophrenia.Phencyclidine-induced increases in glutamate levels in the prefrontal cortex and hyperlocomotion were blocked by 5-HT2A receptor antagonist, an atypical antipsychotic, dozapine. Lesioning the mediodortsal thalamus, which projects the glutamatengic neuronal terminals to the prefrontal cortex, enhanced the behavioral and neurochemical changes of NMDA receptor antagonist, MK-801. Chronic administration of an another atypical antipsychotic, olanzapine increased protein level of dopamine D1 receptors in the prefrontal cortex, enhanced working memory of rats.Therefore, atypical antipsychotics, which can enhance the function of NMDA receptor and dopamine D1 receptor in the prefrontal cortex, may have a potential for improving the cognitive dysfunction of schizophrenia.