Roberts Brooke M, Shaffer Christopher L, Seymour Patricia A, Schmidt Christopher J, Williams Graham V, Castner Stacy A
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
Neuroreport. 2010 Mar 31;21(5):390-4. doi: 10.1097/WNR.0b013e3283381a4e.
Glycine transporter inhibitors have recently been reported to improve symptoms in patients with schizophrenia. Here we used acute ketamine in the nonhuman primate to test the effectiveness of the novel glycine transporter inhibitor, PF-3463275, in a model of cognitive dysfunction relevant to schizophrenia. PF-3463275 (0.01-0.17 mg/kg; subcutaneously) or a vehicle was given before the administration of ketamine (median dose of 1.0 mg/kg intramuscularly) or placebo (saline). Ketamine induced hallucinatory-like behaviors that were not reversed by PF-3463275. In contrast, all doses of PF-3463275 alleviated the deficit in spatial working memory induced by ketamine. Theses findings build upon those in patients by providing translational support for targeting glycine transporter in adjunctive treatment for cognitive dysfunction in schizophrenia.
最近有报道称，甘氨酸转运体抑制剂可改善精神分裂症患者的症状。在此，我们在非人类灵长类动物中使用急性氯胺酮，以在与精神分裂症相关的认知功能障碍模型中测试新型甘氨酸转运体抑制剂PF-3463275的有效性。在给予氯胺酮（肌肉注射中位剂量为1.0 mg/kg）或安慰剂（生理盐水）之前，给予PF-3463275（0.01 - 0.17 mg/kg；皮下注射）或赋形剂。氯胺酮诱发的类似幻觉行为未被PF-3463275逆转。相比之下，所有剂量的PF-3463275均减轻了氯胺酮诱发的空间工作记忆缺陷。这些发现基于患者研究结果，为在精神分裂症认知功能障碍辅助治疗中靶向甘氨酸转运体提供了转化支持。
