应激性抑郁样行为发生中海马5-羟色胺1A受体的作用及其对NMDA受体和AMPA受体的调节  

Role of Hippocampal 5-HT1A Receptor and Its Modulation to NMDA Receptor and AMPA Receptor in Depression Induced by Chronic Unpredictable Mild Stress

作　　者：问黎敏[1] 安书成[1] 刘慧[1] 

机构地区：[1]陕西师范大学生命科学学院,西安710062

出　　处：《心理学报》2012年第10期1318-1328,共11页Acta Psychologica Sinica

基　　金：中央高校基本科研业务费专项资金(GK200901011)资助

摘　　要：为探讨慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)诱发抑郁样行为发生中海马5-羟色胺1A受体(5-hydroxytryptamine receptor 1A,5-HT1AR)表达与作用,及其对谷氨酸N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体和α-氨基羟甲基异恶唑丙酸(α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid,AMPA)受体的影响。通过建立CUMS动物模型,给应激抑郁模型大鼠海马微量注射5-HT1A受体激动剂、给正常大鼠海马微量注射5-HT1A受体拮抗剂,测量大鼠体重变化率,并采用糖水偏爱测试、旷场实验和悬尾实验等方法对大鼠进行行为学检测,运用Western blot和ELISA方法检测大鼠海马组织中5-HT1AR和NMDAR和AMPAR的关键亚基的表达以及磷酸化水平。结果显示,与对照组相比,CUMS组大鼠表现出抑郁样行为,海马5-HT1AR、AMPA受体的GluR2/3亚基表达及磷酸化明显降低,NMDA受体的NR1和NR2B亚基表达及磷酸化显著增加;正常大鼠海马微量注射5-HT1A受体拮抗剂WAY100635,动物行为学表现及AMPA受体、NMDA受体表达及磷酸化水平均与CUMS组相同;注射5-HT1A受体激动剂8-OH-DPAT能逆转应激诱导的上述改变。以上结果表明,CUMS诱发抑郁样行为与海马5-HT1AR表达下降,AMPAR表达量及磷酸化水平降低,NMDAR表达量及磷酸化水平升高有关。5-HT通过5-HT1AR产生抗抑郁作用。5-HT1AR激动剂抗抑郁作用与降低NMDAR表达量及磷酸化水平,提高AMPAR表达量及磷酸化水平密切相关。Stressors markedly influence central neurochemical and hormonal processes and thus play a pivotal role in the occurrence of depressive illnesses. As the center for stress response and the potential target for stressful provocation, the hippocampus is becoming a focus in depression research. Although a large number of behavioral paradigms have been proposed as animal models of depression, only a few are considered potentially useful research tools with sufficient validity. The most accepted one is the chronic unpredictable mild stress （CUMS） rodent model, in which rats are chronically and unpredictably subjected to a variety of stressors including immersion in cold water, tail pinch, day and night reversal, and so on. There are several theoretical mechanisms for depression, such as the monoamine neurotransmitter imbalance theory and the neural plasticity theory, but none of them can fully elucidate the formation of depression. Due to the weak and irregular anti-depressant effects of monoamines, glutamate （Glu） and its receptors, especially N-methyl-D-aspartic acid （NMDA） receptors and ct-amino-3-hydroxy-5-methylisoxazole-4- propionic acid （AMPA） receptors, have gained more attention in recent years. As an important isoform of the 5-hydroxytryptamine （5-HT） receptor, the 1A receptor is highly expressed in the hippocampus. Numerous pharmacological and clinical studies show that the 1A receptor is correlated with the development and therapy of major depressive disorder, anxiety, and drug addiction. The present study investigates the expression and role of the 5-HT receptor 1A （5-HT1AR） and its relationship with NMDA and AMPA receptors in depression induced by CUMS. The CUMS induced depression model was done using Sprague-Dawley rats that were given intra-hippocampal microinjections of drugs. The location of injections was determined by rat brain stereotaxic coordinates. The behavioral observations were conducted by measurement of weight changes, sucrose preference test, open-field test, and t

关 键 词：慢性不可预见性温和应激 抑郁症 海马 5-HT1A受体 NMDA受体 AMPA受体 

分 类 号：B845[哲学宗教—心理学]