慢性应激抑郁模型大鼠脑内5HT_(1A)和5-HT_(2A)受体的变化  

Changes of 5-HT_(1A) receptor and 5-HT_(2A) receptors in the brain of rat with stress-induced depression

作　　者：刘效巍[1] 许晶[1] 李晓秋[1] 张慧[1] 王俊平[1] 左萍萍[2] 杨楠[2] 

机构地区：[1]大连医科大学附属第一医院神经内科,大连116011 [2]中国医学科学院中国协和医科大学基础医学研究所药理学教研室,北京100005

出　　处：《基础医学与临床》2004年第2期174-178,共5页Basic and Clinical Medicine

基　　金：辽宁省科委自然科学基金 (0 0 2 0 6 3)

摘　　要：为了在 5 羟色胺受体水平研究抑郁症的机制和三环类抗抑郁药物 (TCAs)阿米替林的药理学机理 ,将 2 4只SD雄性大鼠随机均分为三组 ,即对照组、抑郁组、阿米替林治疗组。应用 [3H]8 OH DPAT、[3H]Ketanserin作为标记配基 ,采用放射性配体受体结合法 ,分别测定大鼠海马 5 HT1A受体、大脑皮层 5 HT2A 受体结合。结果显示 :抑郁大鼠海马 [3H]8 OH DPAT特异性结合 (1 8 78± 5 6 2fmol mgprot) ,较正常对照组 (2 6 1 2± 5 5 2fmol mgprot )明显下降(P <0 0 5 )。抑郁大鼠大脑皮层 [3H]Ketanserin特异性结合 (1 1 2 5 8± 4 2 1fmol mgprot) ,较正常对照组 (86 2 8±4 2 4fmol mgprot)明显增加 (P <0 0 5 )。阿米替林治疗 3周后 ,可使抑郁大鼠海马 5 HT1A 受体与大脑皮层 5 HT2A 受体结合恢复正常。提示 :海马 5 HT1A受体结合下降、大脑皮层 5 HT2A 受体结合增加可能与抑郁症病因有关 ;海马 5 HT1A 受体、大脑皮层 5 HT2A 受体是阿米替林发挥抗抑郁作用的环节。To investigate the pharmacological mechanism of Amitriptyline on the serotonin receptor level in depression induced by unpredicted mild stress ,24 male Sprague Dawley rats were randomly divided into three groups:control,depression and depression treated with Amitriptyline. [ 3 H]8 OH DPAT and[ 3 H]Ketanserin as radioactive ligands were respectively used in testing special binding of 5 HT 1A receptor in the hippocampus or 5 HT 2A receptor in cerebral cortex. The results showed that the special binding of 5 HT 1A R in experimental group [(18.78±5.62)fmol/mg protein ]decreased as compared to that in control group[(26.12±5.52) fmol/mg protein, P <0.05].The special binding of 5 HT 2A R in experimental group[(112.58±4.21)fmol/mg protein]increased vs control group[(86.28±4.24)fmol/mg protein, P <0 05] .After amitriptyline treatment for three weeks, the special binding of 5 HT 1A receptor and 5 HT 2A receptor in experimental group obviously recovered to the normal level ( P <0.05).These results suggested that the changes of 5 HT 1A R in hippocampus and 5 HT 2A R in cerebral cortex may play a role in the pathogenesis of depressive disorder. The increased 5 HT 1A R in hippocampus and decreased 5 HT 2A R may also be related to the therapeutic effect of the Amitriptyline in depressive disorder.

关 键 词：抑郁症 应激 5-HT1A受体 5-HT2A受体 阿米替林 

分 类 号：R749.4[医药卫生—神经病学与精神病学]