CAJ | 학술논문

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（glutamicacid，Glu）及其N-甲基-D-天冬氨酸（N．methyl．D．asparticacid，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（chronicunpredictablemildstress，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-performanceliquidchromatography,HPLC）和蛋白质免疫印迹法（Westernblot，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。
본문지재탐토만성응격성억욱발생과정중광액협다파알D1수체대곡안산（glutamicacid，Glu）급기N-갑기-D-천동안산（N．methyl．D．asparticacid，NMDA）수체적NR2B아기적영향。실험통과건립만성불가예견성온화응격（chronicunpredictablemildstress，CUMS）억욱모형，결합광액협미량주사다파알D1수체격동제SKF38393화다파알D1수체길항제SCH23390，운용당수편애측시、현미실험화창상실험등방법검측동물적행위표현，채용고효액상색보법（high-performanceliquidchromatography,HPLC）화단백질면역인적법（Westernblot，WB）래검측광액협내곡안산、다파알함량급NR2B화다파알D1수체적표체。결과현시，여대조조상비，CUMS조대서표현출명현적억욱양행위변화，차광액협다파알함량강저，기D1형수체표체강저，곡안산함량승고，기NMDA수체적NR2B아기야명현상조；주사SKF38393후가명현개선응격인기적억욱양행위，차광액협곡안산함량현저하강，NMDA수체적NR2B아기표체야유소강저；정상대서주사다파알D1수체길항제SCH23390，대서표현출화CUMS모형조상사적억욱양행위，차광액협곡안산함량승고，기NMDA수체적NR2B아기야명현상조。이상결과표명，만성불가예견성응격가능사광액협다파알석방감소，종이사곡안산과량석방，NMDA수체과도격활，도치억욱발생。다파알항억욱작용시통과D1형수체억제곡안산급기NMDA수체NR2B아기표체래실현。
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 ofNR2B 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 D I 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.