海马多巴胺D1受体激活抑制谷氨酸介导的大鼠慢性应激性抑郁  

Activation of hippocampal D1 dopamine receptor inhibits glutamate-mediated depression induced by chronic unpredictable mild stress in rats

作　　者：原婷婷[1] 乔卉[1] 董素平[1] 安书成[1] 

机构地区：[1]陕西师范大学生命科学学院,西安710062

出　　处：《生理学报》2011年第4期333-341,共9页Acta Physiologica Sinica

基　　金：supported by the Fundamental Research Funds for the Central University of China(No.GK200901011)

摘　　要：本文旨在探讨在慢性应激性抑郁发生过程中多巴胺D1受体对谷氨酸及其离子型受体的影响。实验通过建立慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)抑郁模型,结合海马微量注射多巴胺D1受体激动剂SKF38393、非竞争性N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体拮抗剂MK-801和α-氨基羟甲基异恶唑丙酸(α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid,AMPA)受体的拮抗剂NBQX,运用糖水偏爱测试、旷场实验和悬尾实验等方法检测动物的行为表现,采用高效液相色谱法(high-performance liquid chromatography,HPLC)和Western blot实验来检测海马内谷氨酸含量及其离子型受体关键亚基的表达。结果显示,与对照组相比,CUMS组大鼠表现出明显的抑郁样行为变化,且海马谷氨酸含量升高,其NMDA受体的NR1亚基与AMPA受体的GluR2/3亚基也明显下调;注射SKF38393后可明显改善应激引起的抑郁样行为,且海马谷氨酸含量显著下降,NMDA受体的NR1亚基与AMPA受体的GluR2/3的表达也有所增加;联合注射MK-801能加强SKF38393的抗抑郁作用,而NBQX则能减弱SKF38393的抗抑郁效应。以上结果表明,多巴胺D1受体激动剂可以通过降低大鼠海马谷氨酸的含量起到抗应激性抑郁的作用,其抗抑郁作用与MK-801协同,部分通过调制AMPA受体实现。The present study was to investigate the role of dopamine D1 receptors and its relationship with glutamate, N-methyl-Daspartic acid （NMDA） receptor and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid （AMPA） receptor in depression induced by chronic unpredictable mild stress （CUMS）. CUMS-induced depression model was established in Sprague-Dawley rats, and intrahippocampal microinjections of D1 dopamine receptor agonist SKF38393, non-competitive NMDA receptor antagonist MK-801 and AMPA receptor antagonist NBQX were respectively adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by measurement of weight changes, sucrose preference test, open-field test and tail suspension test. The concentration of glutamic acid and the expression of its receptors’ subunits were detected by HPLC and Western blot, respectively. The results showed that, compared with control group, CUMS rats showed depression-like behavioral changes, higher concentration of glutamic acid, lower expressions of NMDA receptor （NR1） and AMPA receptor （GluR2/3） in hippocampus. Pretreatment with injection of SKF38393 could rescue such depression effect of CUMS, decrease the concentration of glutamic acid, and increase the expressions of NMDA receptor （NR1）, AMPA receptor （GluR2/3） in hippocampus. Pretreatment with MK-801 could enhance the antidepressant effect of SKF38393, while NBQX weakened. These results suggest that agonists of D1 dopamine receptor could reduce the concentration of glutamic acid in hippocampus, and its antidepressant effect may be mediated by AMPA receptor partially.

关 键 词：应激 抑郁症 海马 多巴胺D1受体 AMPA受体 NMDA受体 

分 类 号：R749.4[医药卫生—神经病学与精神病学]