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[Involvement of hippocampal NMDA receptor and neuropeptide Y in depression induced by chronic unpredictable mild stress.] [Ariticle in Chinese]

YU Ling, AN Shu-Cheng^*, LIAN Ting

College of Life Science, Shaanxi Normal University, Xi'an 710062, China

Abstract

The present study was aimed to investigate the role and relationship between N-methyl-D-aspartic acid (NMDA) receptorand neuropeptide Y (NPY) in depression induced by chronic unpredictable mild stress (CUMS). CUMS-induced depression modelwas established in Sprague-Dawley rats. Intrahippocampal injections of NMDA, non-competitive NMDA receptor antagonist MK-801 and NPY-Y1 receptor antagonist GR231118 were respectively adopted by rat brain stereotaxic coordinates. The behavioralobservations were conducted by sucrose consumption test, open field test and forced swimming test. The expression of NPY inhippocampus was detected by immunohistochemistry. The results showed that compared with the control group, rats receivingCUMS for 21 days or intrahippocampal injection of GR231118 or NMDA showed depression-like behavioral changes, including areduction in sucrose preference, body weight, locomotor activity, rearing and grooming in open field test, and increased duration ofimmobility in forced swimming test. Intrahippocampal injection of NMDA decreased the expression of NPY in hippocampal CA3region and dentate gyrus (DG) region. Intrahippocampal injection of MK-801 improved the depression-like behavioral changes inducedby CUMS, and increased the expression of NPY in hippocampal CA3 region and DG region. Co-injection of GR231118 and MK-801showed that GR231118 suppressed the antidepressant effect of MK-801. These data suggest that CUMS might induce depressionthrough excessive release of glutamate (Glu), over-activation of NMDA receptors, and downregulation of NPY. Antidepressant effectof NPY was mainly mediated via NPY-Y1 receptor.

Key words: chronic unpredictable mild stress; depression; hippocampus; N-methyl-D-aspartic acid receptor; neuropeptide Y

Received: 2009-11-12　　Accepted: 2010-01-11

Corresponding author: 安书成　　E-mail: shuchengan@snnu.edu.cn

Citing This Article：

YU Ling, AN Shu-Cheng, LIAN Ting. [Involvement of hippocampal NMDA receptor and neuropeptide Y in depression induced by chronic unpredictable mild stress.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (1): 14-22 (in Chinese with English abstract).