文拉法辛对慢性束缚应激大鼠焦虑和抑郁样行为的影响
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摘要
目的探讨文拉法辛对慢性束缚应激大鼠焦虑和抑郁样行为的影响。方法 36只SD大鼠随机分为对照组、模型组、文拉法辛组,每组12只。除对照组外,其余两组大鼠均给予21 d的慢性束缚应激,于每天同一时间段束缚6 h,文拉法辛组在造模同时灌胃给药(6. 75 mg/kg),对照组和模型组给予蒸馏水。采用高架十字迷宫和场景恐惧测试大鼠的焦虑行为,旷场和强迫游泳实验检测大鼠的抑郁行为,HE染色观察大鼠海马组织形态变化,HPLCECD法检测海马单胺递质5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)的含量,ELISA法检测血浆HPA轴促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质酮(CORT)水平。结果模型组大鼠焦虑和抑郁样行为明显(P<0. 01),海马组织存在神经元缺失、排列紊乱、部分胞体呈空泡状等病理现象,5-HT、NE、DA含量均明显下调(P<0. 05),血浆CRH、ACTH、CORT水平显著升高(P<0. 01);经文拉法辛治疗后,大鼠焦虑及抑郁样均有较明显的缓解(P<0. 05),海马神经元损伤减轻,5-HT、NE、DA含量均有不同程度的上升(P<0. 05),血浆CRH、ACTH、CORT水平下降(P<0. 05)。结论文拉法辛能明显改善慢性束缚应激大鼠焦虑和抑郁样行为,缓解海马神经元损伤,其作用可能与上调脑内单胺神经递质含量,抑制体内HPA轴过度亢进有关。
Objective To explore the effects of venlafaxine on anxiety and depression-like behavior in rats with chronic restraint stress. Methods Thirty-six SD rats were randomly divided into control,model,and venlafaxine groups,with 12 rats in each group. The model and venlafaxine groups were given chronic restraint stress for 21 days,and were restrained for 6 hours at the same time every day. Venlafaxine was administered intragastrically( 6. 75 mg/kg),and the control and model groups were given distilled water intragastrically. Rats were tested for anxiety using the elevated plus maze and scene fear test. Depression behavior was tested using the open field and forced swimming tests. Hematoxylin and eosin( HE) staining was used for the pathological examination of the rat hippocampus. A high performance liquid chromatography-electrochemical method was used to measure the content of 5-HT,NE and DA in the hippocampus,and plasma HPA axis CRH,ACTH and CORT levels were detected by ELISA. Results Anxiety and depression-like behaviors in the model group were significant( P<0. 01). Pathological changes such as neuron loss,disordered arrangement,and vacuolization of some cells were observed in the hippocampus of model rats. The contents of 5-HT,NE and DA were significantly downregulated( P<0. 05),and plasma CRH,ACTH,and CORT levels were significantly increased in the model group( P<0. 01). Compared with the model group,after treatment with venlafaxine,anxiety and depression were significantly relieved( P< 0. 05),hippocampal neuron injury was alleviated,the contents of 5-HT,NE and DA were increased to different degrees( P< 0. 05),and plasma CRH,ACTH,and CORT levels were decreased( P < 0. 05). Conclusions Venlafaxine significantly improve anxiety and depression-like behaviors in rats with chronic restraint stress,and alleviate hippocampal neuronal damage,which might be related to the upregulation of monoamine neurotransmitters in the brain and inhibiting excessive HPA axis stimulation in vivo.
Objective To explore the effects of venlafaxine on anxiety and depression-like behavior in rats with chronic restraint stress. Methods Thirty-six SD rats were randomly divided into control,model,and venlafaxine groups,with 12 rats in each group. The model and venlafaxine groups were given chronic restraint stress for 21 days,and were restrained for 6 hours at the same time every day. Venlafaxine was administered intragastrically( 6. 75 mg/kg),and the control and model groups were given distilled water intragastrically. Rats were tested for anxiety using the elevated plus maze and scene fear test. Depression behavior was tested using the open field and forced swimming tests. Hematoxylin and eosin( HE) staining was used for the pathological examination of the rat hippocampus. A high performance liquid chromatography-electrochemical method was used to measure the content of 5-HT,NE and DA in the hippocampus,and plasma HPA axis CRH,ACTH and CORT levels were detected by ELISA. Results Anxiety and depression-like behaviors in the model group were significant( P<0. 01). Pathological changes such as neuron loss,disordered arrangement,and vacuolization of some cells were observed in the hippocampus of model rats. The contents of 5-HT,NE and DA were significantly downregulated( P<0. 05),and plasma CRH,ACTH,and CORT levels were significantly increased in the model group( P<0. 01). Compared with the model group,after treatment with venlafaxine,anxiety and depression were significantly relieved( P< 0. 05),hippocampal neuron injury was alleviated,the contents of 5-HT,NE and DA were increased to different degrees( P< 0. 05),and plasma CRH,ACTH,and CORT levels were decreased( P < 0. 05). Conclusions Venlafaxine significantly improve anxiety and depression-like behaviors in rats with chronic restraint stress,and alleviate hippocampal neuronal damage,which might be related to the upregulation of monoamine neurotransmitters in the brain and inhibiting excessive HPA axis stimulation in vivo.
引文
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[11]韩远山,赵洪庆,杨蕙,等.左归降糖解郁方对糖尿病并发抑郁症大鼠HPA轴及海马糖皮质激素受体表达的影响[J].中国中医基础医学杂志,2017,23(12):1710-1713.
[12]苑杰,许冬稳,曹洋洋,等.焦虑症的生化病理机制探讨[J].中国继续医学教育,2015,27(7):71-72.
[13] Motaghinejad M,Motevalian M,Shabab B. Effects of chronic treatment with methylphenidate on oxidative stress and inflammation in hippocampus of adult rats[J]. Neurosci Lett,2016,619(6):106-113.
[14]赵洪庆.焦虑性抑郁动物模型及其多层次评价体系的建立[D].长沙:湖南中医药大学,2017.
[2] Meier SM, Petersen L, Mattheisen M, et al. Secondary depression in severe anxiety disorders:a population-based cohort study in Denmark[J]. Lancet Psychiatry,2015,2(6):515-523.
[3] Chiba S,Numakawa T,Ninomiya M,et al. Chronic restraint stress causes anxiety-and depression-like behaviors,downregulates glucocorticoid receptor expression,and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex[J]. Prog Neuropsychopharmacol Biol Psychiatry,2012,39(1):112-119.
[4] Lehner M,Wislowska-Stanek A, Gryz M, et al. The coexpression of GluN2B subunits of the NMDA receptors and glucocorticoid receptors after chronic restraint stress in low and high anxiety rats[J]. Behav Brain Res,2017,319(12):124-134.
[5]赵洪庆,韩远山,杜青,等.不同时间点不同应激方法致大鼠焦虑样行为的研究[J].中国比较医学杂志,2017,27(1):22-26.
[6] Gibbons RD, Hur K, Brown CH, et al. Benefits from antidepressants:synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine[J]. Arch Gen Psychiatry,2012,69(6):572-579.
[7] Nautiyal KM,Hen R. Serotonin receptors in depression:from A to B[J]. F1000Res,2017,6:123.
[8] Dale E,Pehrson AL,Jeyarajah T,et al. Effects of serotonin in the hippocampus:how SSRIs and multimodal antidepressants might regulate pyramidal cell function[J]. CNS Spectr,2016,21(2):143-161.
[9] Belujon P,Grace AA. Dopamine system dysregulation in major depressive disorders[J]. Int J Neuropsychopharmacol,2017,20(12):1036-1046.
[10]赵洪庆,韩远山,柳卓,等.焦虑性抑郁模型大鼠脑区单胺递质含量与神经因子表达的变化[J].中国实验动物学报,2017,25(4):373-379.
[11]韩远山,赵洪庆,杨蕙,等.左归降糖解郁方对糖尿病并发抑郁症大鼠HPA轴及海马糖皮质激素受体表达的影响[J].中国中医基础医学杂志,2017,23(12):1710-1713.
[12]苑杰,许冬稳,曹洋洋,等.焦虑症的生化病理机制探讨[J].中国继续医学教育,2015,27(7):71-72.
[13] Motaghinejad M,Motevalian M,Shabab B. Effects of chronic treatment with methylphenidate on oxidative stress and inflammation in hippocampus of adult rats[J]. Neurosci Lett,2016,619(6):106-113.
[14]赵洪庆.焦虑性抑郁动物模型及其多层次评价体系的建立[D].长沙:湖南中医药大学,2017.