海马NMDA受体经SP-NK1受体通路参与慢性应激诱发的抑郁样行为  

Hippocampal NMDA Receptor is involved in Chronic Stress Induced Depressive-Like Behaviors via SP-NK1 Receptor Pathway

作　　者：董素平[1] 徐畅[1] 原婷婷[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：《心理学报》2011年第9期1045-1054,共10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：为探讨海马N-甲基-D-天冬氨酸(N-methyl-D-asparticacid,NMDA)受体与P物质(SubstanceP,SP)及其神经激肽1(neuro kinin1,NK1)受体在慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)中的作用及其关系,通过建立CUMS动物模型,大鼠海马微量注射给药,测量大鼠体重,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,运用高效液相色谱(HPLC)法分析大鼠海马组织中SP和谷氨酸(glutamate,Glu)的含量变化。结果显示,CUMS诱发大鼠表现出明显的抑郁样行为,海马组织中SP和Glu水平显著增加;海马注射NMDA,大鼠表现出与CUMS/SAL组相似的抑郁样行为,且海马组织中SP的含量比正常对照组显著增加;微量注射NK1受体阻断剂CP-96345和/或NMDA受体阻断剂MK-801后,大鼠抑郁样行为明显改善,且MK-801使CUMS导致的大鼠海马P物质水平升高得到明显控制,而CP-96345没有明显改变CUMS引起的海马Glu水平升高;CP-96345使NMDA引起的抑郁样行为得到极显著改善。以上结果表明,慢性应激引起大鼠海马Glu过量释放,通过激活NMDA受体,促进P物质合成释放增加,激活NK1受体,是导致抑郁样行为发生的重要途径之一。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,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 as potentially useful research tools with sufficient validity.The most accepted one is chronic unpredictable mild stress rodent model,in which rats were subjected chronically and unpredictably to a variety of stressors including immersion in cold water,tail pinch,day and night reversed and so on.There are several theoretic mechanisms for depression,such as monoamine neurotransmitter imbalance theory,neural plasticity theory,but none of them can fully elucidate the formation of depression.Due to weakness of the antidepressant-like effect of monoamines,glutamate（Glu） and its receptors,especially N-methyl-D-aspartic acid（NMDA） receptor,and neuropeptides such as neuropeptide Y（NPY）,substance P（SP）,are drawing closer attention in recent years.Here,we are attempted to explore the interaction between Glu/NMDA receptor and SP/neurokinin 1（NK1） receptor in chronic unpredictable mild stress（CUMS）-induced depression.CUMS-induced depression model was established in 250~300g weighted 90-day old Sprague-Dawley rats.Intrahippocampal microinjection of NK1 receptor antagonist CP-96345,NMDA receptor agonist NMDA or NMDA receptor antagonist MK-801 was performed under stereotaxic guide cannula.The body weight of rats was weighed on the 1st,7th,14th,and 21st days during the experiment.The behavioral conducts were observed by means of sucrose consumption test,open field test and tail suspension test.The substance P（SP） and glutamate（Glu） content in hippocampus were separately determined by High performance liquid chromatography（HPLC）.One-way ANOVA,LSD and repeated measures in SPSS were used in datu

关 键 词：慢性不可预见性温和应激 抑郁症 海马 NMDA受体 P物质 

分 类 号：B845[哲学宗教—心理学] Q427[生物学—神经生物学]