Persisting cognitive deficits induced by low-dose, subchronic treatment with MK-801 in adolescent rats
Persisting cognitive deficits induced by low-dose, subchronic treatment with MK-801 in adolescent rats
复制标题
青春期大鼠低剂量、亚慢性治疗 MK-801 诱导的持续认知缺陷
DOI：
10.1016/j.ejphar.2010.10.074
复制
发表时间：
2011-02-10
影响因子：
5
通讯作者：
Si, Tian-Mei
中科院分区：
文献类型：
--
作者：
Li, Ji-Tao;Su, Yun-Ai;Si, Tian-Mei
认知障碍被认为是精神分裂症的核心特征。研究表明，慢性或亚慢性N-甲基-D-天冬氨酸（NMDA）拮抗剂治疗可诱导类似精神分裂症症状的认知缺陷，但很少有研究调查青春期重复NMDA阻断对认知的影响。在当前研究中，对青春期雄性大鼠腹膜内注射MK-801（0.05、0.1和0.2 mg/kg），每日一次，持续14天。然后，在停药后24小时和14天，分别对他们进行一系列行为任务的测试，包括物体识别任务、情境中物体识别任务和莫里斯水迷宫（MWM）的工作记忆任务。结果表明，当动物在停药后24小时接受检测时，MK-801重复给药显著损害了MWM中的上下文对象识别和空间工作记忆，但对象识别保持完整。特别是，在0.2 mg/kg组停药后14天观察到此类缺陷。MK-801的认知损害效应不能归因于营养不良或运动功能改变。综上所述，本研究可能为建立基于MK-801在青春期低剂量重复治疗的精神分裂症认知缺陷动物模型提供支持。(C)出版社：Elsevier B. V.
Cognitive impairments have been proposed as a core feature of schizophrenia. Studies have shown that chronic or subchronic treatment with N-methyl-D-aspartate (NMDA) antagonists could induce cognitive deficits that resemble the symptoms of schizophrenia, yet few studies have investigated the effects of repeated NMDA blockade during adolescence on cognition. In the current study, adolescent, male rats were treated with an intraperitoneal injection of MK-801 (0.05, 0.1, and 0.2 mg/kg) once daily for 14 days. They were then tested 24 h and 14 days after drug cessation, respectively, in a series of behavioural tasks, including the object recognition task, the object-in-context recognition task and the working memory task of the Morris water maze (MWM). Results showed that object-in-context recognition and spatial working memory in the MWM were significantly impaired by repeated MK-801 treatment when animals were tested 24 h after drug cessation, but object recognition was left intact. In particular, such deficits were observed 14 days after drug cessation in the 0.2 mg/kg group. The cognition-impairing effect of MK-801 could not be attributed to malnutrition or alterations in motor functions. Taken together, this study may provide support for establishing an animal model of cognitive deficits of schizophrenia based on low-dose, repeated treatment of MK-801 during adolescence. (C) 2010 Published by Elsevier B.V.