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目的 探讨慢性皮质酮注射对近灵长类动物树闙焦虑和抑郁样行为的影响,并进行药物预见性评价,建立新型焦虑性抑郁动物模型。方法 12只中缅树闙随机分为正常组、模型组和文拉法辛组,每组4只。采用慢性皮质酮注射(ih,27mg·kg~(-1),21d)建立焦虑性抑郁树闙模型,文拉法辛组于造模同时灌胃给药(6mg·kg~(-1))。采用自主活动评分、糖水偏好测试、Morris水迷宫实验评价树闙的焦虑和抑郁行为表现;ELISA试剂盒检测树闙血浆CRH、ACTH、COR含量;HPLC-ECD法检测树闙脑内海马、杏仁核、前额叶皮质的单胺递质5-HT、NE、DA含量。结果 与正常组比较,模型组树闙自主活动评分、糖水偏食度、学习记忆能力均明显下降(P<0.01),血浆CRH、ACTH、COR含量明显上升(P<0.05),海马、杏仁核、前额叶皮质5-HT、NE、DA含量降低(P<0.05);文拉法辛组树闙学习记忆能力得到改善,血浆CRH、COR含量明显降低(P<0.05),各脑区5-HT、NE、DA含量上升(P<0.05)。结论 焦虑性抑郁模型树闙具有明显的HPA轴亢进及单胺递质失调现象,而文拉法辛能够逆转该现象,说明该焦虑性抑郁树闙模型具有药物预见性,是一种更接近人类临床的新型焦虑性抑郁动物模型。
Objective To investigate the effects of chronic corticosterone injection on the anxiety and depression-like behavior of tree primate in near-primates and to evaluate the drug’s predictive value and establish a new animal model of anxiety depression. Methods Twelve trees were randomly divided into normal group, model group and venlafaxine group, with 4 in each group. The model of anxiety depression was established by chronic corticosterone injection (ih, 27 mg · kg -1, 21 d). The venlafaxine group was administered intragastrically (6 mg · kg -1) . The activity of anxiety and depression in the tree shrews were evaluated by voluntary activity score, sugar preference test and Morris water maze test. CRH, ACTH and COR contents in the tree shrew plasma were detected by ELISA kit. The hippocampus and amygdala , Prefrontal cortex monoamine neurotransmitters 5-HT, NE, DA content. Results Compared with the normal group, the scores of spontaneous activity of tree 闙, degree of glycohydral edema, learning and memory ability of model group were significantly decreased (P <0.01), while the contents of CRH, ACTH and COR were significantly increased (P <0.05) The contents of 5-HT, NE and DA in the prefrontal cortex decreased (P <0.05), while the venlafaxine group improved the ability of learning and memory, and the levels of plasma CRH and COR were significantly decreased (P <0.05) , NE, DA increased (P <0.05). CONCLUSIONS: The anxiety depression model tree 闙 has obvious hyperactivity of HPA axis and monoamine neurotransmitter imbalance, whereas venlafaxine reverses this phenomenon, indicating that the anxiety depression tree 闙 model is drug-predictive and is closer to human Clinical New Anxiety Depression Animal Model.