Impaired working memory by repeated neonatal MK-801 treatment is ameliorated by galantamine in adult rats

被引：26
|
作者：
Su, Yun-Ai [1 ,2 ]
Huang, Run-Hu [1 ,2 ,3 ]
Wang, Xiao-Dong [1 ,2 ]
Li, Ji-Tao [1 ,2 ]
Si, Tian-Mei [1 ,2 ]
机构：
[1] Peking Univ, Minist Hlth, Key Lab Mental Hlth, Beijing 100871, Peoples R China
[2] Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China
[3] Shanxi Dayi Hosp, Taiyuan, Shanxi Province, Peoples R China
来源：
EUROPEAN JOURNAL OF PHARMACOLOGY | 2014年 / 725卷
基金：
高等学校博士学科点专项科研基金;
关键词：
Schizophrenia; Working memory; MK-301; Galantamine; ALLOSTERIC POTENTIATING LIGAND; SCHIZOPHRENIC-PATIENTS; COGNITIVE FLEXIBILITY; KYNURENIC ACID; ACETYLCHOLINE-RECEPTOR; NICOTINIC AGONIST; BRAIN-DEVELOPMENT; NMDA RECEPTORS; BLOCKADE; DEFICITS;
D O I：
10.1016/j.ejphar.2014.01.007
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Early life blockade of the NMDA receptor by using MK-801, a non-competitive NMDA receptor antagonist, induces behavioral changes that mimic several features of schizophrenia. In the current study, we first examined the effects of neonatal MK-801 treatment in male Sprague-Dawley rats on locomotor activity, prepulse inhibition and spatial working memory in adolescence (postnatal day 35, PND35) and adulthood (PND63). Next, we investigated the effects of an acetylcholinesterase inhibitor, galantamine, on working memory deficits induced by MK-801 treatment. Rats were treated with either saline or MK-801 (0.25 mg/kg twice daily) at PND 5-14, and the long-term behavioral effects were investigated. MK-801 treated rats showed moderate working memory impairments in adolescence but a pronounced deficit in adulthood. However, locomotion and prepulse inhibition at two life stages were not affected by this treatment. Systemic administration of galantamine (1 mg/kg) 30 min before each training session significantly improved neonatal MK-801-induced working memory deficits in adulthood. In conclusion, these results suggest that the neonatal MK-801 treatment-induced selective working memory deficit is related to a change in brain cholinergic systems. (C) 2014 Elsevier B.V. All rights reserved
引用
收藏
页码：32 / 39
页数：8
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