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

被引:12
作者
问黎敏
安书成
刘慧
机构
[1] 陕西师范大学生命科学学院
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;
D O I
暂无
中图分类号
B845 [生理心理学];
学科分类号
040203 ;
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。
引用
收藏
页码:1318 / 1328
页数:11
相关论文
共 35 条
  • [21] Opposing effects of AMPA and 5-HT 1A receptor blockade on passive avoidance and object recognition performance: Correlation with AMPA receptor subunit expression in rat hippocampus[J] . L. Schiapparelli,A.M. Simón,J. Del Río,D. Frechilla.Neuropharmacology . 2006 (7)
  • [22] Stress, depression, and anhedonia: Caveats concerning animal models[J] . Hymie Anisman,Kim Matheson.Neuroscience and Biobehavioral Reviews . 2005 (4)
  • [23] Serotonin 5-HT 1A , 5-HT 1B , and 5-HT 2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia[J] . Antonio L López-Figueroa,Camille S Norton,Manuel O López-Figueroa,Denise Armellini-Dodel,Sharon Burke,Huda Akil,Juan F López,Stanley J Watson.Biological Psychiatry . 2004 (3)
  • [24] Chronic restraint stress and chronic corticosterone treatment modulate differentially the expression of molecules related to structural plasticity in the adult rat piriform cortex
    Nacher, J
    Pham, K
    Gil-Fernandez, V
    McEwen, BS
    [J]. NEUROSCIENCE, 2004, 126 (02) : 503 - 509
  • [25] Activation of post-synaptic 5-HT 1A receptors in the dorsal hippocampus prevents learned helplessness development[J] . Brain Research . 2003 (1)
  • [26] Regulation of BDNF expression in primary neuron culture by LY392098, a novel AMPA receptor potentiator[J] . B. Legutko,X. Li,P. Skolnick.Neuropharmacology . 2001 (8)
  • [27] Antidepressant effects of ketamine in depressed patients
    Berman, RM
    Cappiello, A
    Anand, A
    Oren, DA
    Heninger, GR
    Charney, DS
    Krystal, JH
    [J]. BIOLOGICAL PSYCHIATRY, 2000, 47 (04) : 351 - 354
  • [28] Alnespirone (S 20499), an Agonist of 5-HT 1A Receptors, and Imipramine Have Similar Activity in a Chronic Mild Stress Model of Depression[J] . Pharmacology, Biochemistry and Behavior . 1999 (4)
  • [29] WAY 100635, a 5-HT 1A receptor antagonist, prevents the impairment of spatial learning caused by blockade of hippocampal NMDA receptors[J] . M Carli,S Silva,C Balducci,R Samanin.Neuropharmacology . 1999 (8)
  • [30] Stimulation of the 5-HT 1A receptor selectively suppresses NMDA receptor-mediated synaptic excitation in the rat visual cortex[J] . Yoshikuni Edagawa,Hiroshi Saito,Kazuho Abe.Brain Research . 1999 (1)