ISSN 0439-755X
CN 11-1911/B
主办:中国心理学会
   中国科学院心理研究所
出版:科学出版社

心理学报 ›› 2014, Vol. 46 ›› Issue (1): 69-78.doi: 10.3724/SP.J.1041.2014.00069

• 论文 • 上一篇    下一篇

慢性应激性抑郁发生中大鼠眶额叶多巴胺D1受体对谷氨酸及其NMDA受体的调节

吴帅;安书成;陈慧彬;李菲   

  1. (陕西师范大学生命科学学院, 西安 710062)
  • 收稿日期:2013-03-18 出版日期:2014-01-25 发布日期:2014-01-25
  • 通讯作者: 安书成
  • 基金资助:

    中央高校基本科研业务费专项资金(GK200901011)资助。

Orbital Frontal Cortex D1 Dopamine Receptor Modulate Glutamate and NMDA Receptor in Depression Induced by Chronic Unpredictable Mild Stress

WU Shuai;AN Shucheng;CHEN Huibin;LI Fei   

  1. (College of Life Science, Shaanxi Normal University, Xi’an 710062, China)
  • Received:2013-03-18 Online:2014-01-25 Published:2014-01-25
  • Contact: AN Shucheng

摘要:

本文旨在探讨慢性应激性抑郁发生过程中眶额叶多巴胺D1受体对谷氨酸(glutamic acid, Glu)及其N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid, NMDA)受体的NR2B亚基的影响。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, 结合眶额叶微量注射多巴胺D1受体激动剂SKF38393和多巴胺D1受体拮抗剂SCH23390, 运用糖水偏爱测试、悬尾实验和敞箱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)和蛋白质免疫印迹法(Western blot, WB)来检测眶额叶内谷氨酸、多巴胺含量及NR2B和多巴胺D1受体的表达。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, 且眶额叶多巴胺含量降低, 其D1型受体表达降低, 谷氨酸含量升高, 其NMDA受体的NR2B亚基也明显上调; 注射SKF38393后可明显改善应激引起的抑郁样行为, 且眶额叶谷氨酸含量显著下降, NMDA受体的NR2B亚基表达也有所降低; 正常大鼠注射多巴胺D1受体拮抗剂SCH23390, 大鼠表现出和CUMS模型组相似的抑郁样行为, 且眶额叶谷氨酸含量升高, 其NMDA受体的NR2B亚基也明显上调。以上结果表明, 慢性不可预见性应激可能使眶额叶多巴胺释放减少, 从而使谷氨酸过量释放, NMDA受体过度激活, 导致抑郁发生。多巴胺抗抑郁作用是通过D1型受体抑制谷氨酸及其NMDA受体NR2B亚基表达来实现。

关键词: 慢性不可预见性温和应激, 抑郁, 眶额叶, 多巴胺D1受体, 谷氨酸

Abstract:

Stressors play a pivotal role in the occurrence of depressive illnesses. Disorders of monoamine neurotransmitters and their receptors may be the fundamental causes of depression. Additionally, abnormal expression of glutamic acid (Glu) and its receptor may be a major reason for depression. Consequently, the study of the relationship between monoamine and glutamic acid neurotransmitter in stress-induced depression has significances to reveal the profound mechanism of depression. NR2B subunits which are highly expressed in the cortex, hippocampus and olfactory bulb, are one of the key subunits of NMDA receptors. Orbital frontal cortex (orbital frontal cortex, OFC), which plays a significant role in higher brain function, such as emotional and complex behavior, is one of the major sub-regions of prefrontal. This study was to investigate the effect of orbital frontal cortex D1 dopamine receptor on Glu and its receptors, especially on NR2B subunits of N-methyl-D-aspartic acid (NMDA) receptors in depression induced by chronic unpredictable mild stress (CUMS). CUMS-induced depression model was established in Sprague-Dawley rats, and intra-orbital frontal cortex microinjections of D1 dopamine receptor agonist SKF38393 and its antagonist SCH23390 were respectively adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by measurement of sucrose preference test, open-field test and tail suspension test. The concentration of Glu and the expression of NR2B subunits in orbital frontal cortex were detected by high-performance liquid chromatography (HPLC) and Western blot (WB) respectively. In comparison to control groups, depression-like behavioral changes were observed in CUMS rats, the concentration of dopamine and its D1 receptor were decreased; conversely, the increase of Glu and NR2B subunits of its NMDA receptors were observed in orbital frontal cortex. Depression-like behavioral of CUMS rats was obviously improved after pretreatment with injection of SKF38393, the expression of Glu and NR2B subunits of its NMDA receptors were also decreased. Normal rats showed depression-like behavioral which similar to the CUMS rats after pretreatment with injection of D1 dopamine receptor antagonist SCH23390, meanwhile, in orbital frontal cortex the expression of Glu and NR2B subunits of its NMDA receptors were significantly increased. These results suggest that the lowered dopamine release may be caused by chronic unpredictable mild stress, as the result of insufficient dopamine, orbital frontal cortex releases extra amounts of glutamic acid and its NMDA receptors are over activated. All those above then may lead to depression. Antidepressant effect of dopamine may be functioned by inhibiting the expression of Glu and NR2B subunits of its NMDA receptors.

Key words: chronic unpredictable mild stress, depression, orbital frontal cortex, D1 dopamine receptor, glutamic acid