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阿司匹林对应激诱导的抑郁样行为及神经生化、内分泌和免疫系统的影响
其他题名Effect of aspirin on depression-like behaviors induced by stress and neurochemical, endocrine and immune systems
管西婷
学位类型硕士
导师王玮文
2011-06
学位授予单位中国科学院研究生院
学位授予地点北京
学位专业心理学
关键词阿司匹林 抑郁样行为 强迫游泳测试 慢性冷水游泳应激
摘要近年来,一些临床和实验动物研究发现阿司匹林可能具有情绪调节作用,但其抗抑郁作用特点及介导途径尚不清楚。本研究分别采用强迫游泳测试和慢性冷水游泳应激两种模式系统考察了阿司匹林对应激诱导的抑郁样行为的影响及其神经生化,内分泌和免疫机理。研究采用强迫游泳测试中的绝望行为、糖精水偏好测试及旷场测试检测大鼠抑郁样行为;采用高架十字迷宫测试检测大鼠焦虑样行为;采用高效液相色谱法检测杏仁核、海马、内侧前额叶、纹状体、外侧隔区去甲肾上腺素和5-羟色胺及其代谢物水平;采用免疫酶联吸附技术检测血清皮质酮及促炎性细胞因子水平。主要研究结果如下: 第一部分:阿司匹林在强迫游泳测试中的抗抑郁作用 阿司匹林剂量依赖地减少强迫游泳测试中的不动行为和增加挣扎行为。阿司匹林增加海马NE水平和大多数所检测脑区的5-羟色胺代谢物(5-HIAA)水平。阿司匹林降低海马5-HT代谢率(5-HIAA/5-HT),但对其他脑区缺乏明显作用。此外,阿司匹林对强迫游泳测试诱导的皮质酮升高缺乏明显作用,但剂量依赖地逆转了应激诱导的IL-6和TNF-α释放增加。上述结果提示阿司匹林在强迫游泳测试中的抗抑郁作用可能通过增强去甲肾上腺素能和5-羟色胺能神经传递以及抑制促炎性因子分泌介导。 第二部分:阿司匹林在慢性冷水游泳应激中的抗抑郁作用 阿司匹林剂量依赖地改善慢性冷水游泳应激导致的糖水偏好指数降低。高剂量阿司匹林特异性减少应激组大鼠高架十字迷宫开臂进入次数和停留时间,提示阿司匹林缓解慢性应激导致的抑郁样行为,但同时高剂量阿斯匹林可能增加应激动物的焦虑水平。然而,慢性冷水游泳应激对所检测脑区的单胺类递质及其代谢物以及外周血皮质酮和促炎性细胞因子IL-6和TNF-α的水平均没有明显作用。阿司匹林对上述单胺类递质,皮质酮和促炎性因子水平的影响也缺乏明显的量效关系,提示它们可能并不在慢性冷水游泳应激诱导的抑郁样行为和阿司匹林治疗中发挥主要作用。 综上,阿司匹林同时改善急性强迫游泳测试和慢性冷水游泳应激诱导的抑郁样行为。脑单胺类递质及促炎性因子可能参与了阿司匹林在强迫游泳测试中的抗抑郁作用,但慢性应激未能引起上述指标的明显改变,它们在慢性应激诱导的抑郁样行为中的作用或其他可能的介导途径尚待证实。
其他摘要Clinical and preclinical studies showed that aspirin may have the effect of emotion regulation, but the mechanisms underlying the antidepressant effect of aspirin remain unknown. In this study, we examined the effect of aspirin on depression-like behaviors and the neurochemical, endocrine and immune responses induced by acute forced swim test (FST) and chronic cold water swim (CCWS). Depression-like behaviors were detected by the despair behavior in FST, saccharin preference test and open field test. Anxiety-like behaviors were tested in elevated plus-maze (EPM). The high performance liquid chromatographic method was used to determine the level of monoamines and their metabolites in different brain areas. ELISA was used to determine the level of corticosterone and pro-inflammation cytokines in serum. The main results were as follows: Part One: The antidepressant effect of aspirin in FST and its mechanisms. Aspirin decreased immobility behavior and increased climbing behavior in FST depending on dosage. Aspirin increased the level of norepinephrine (NE) in hippocampus (HIP) and 5-hydroxyindole acetic acid (5-HIAA, the metabolite of serotonin) in most brain areas tested. In addition, aspirin had no effects on the metabolic rate of 5- hydroxytryptamine (5-HT) (5-HIAA/5-HT) in all tested brain regions except HIP. FST increased the release of corticosterone and pro-inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in peripheral blood. Aspirin showed no significant effect on the increased corticosterone response in FST, but reversed the increase of IL-6 and TNF-α relying on dosage. These results suggested that aspirin might exert antidepressant effect in FST via increasing NEergic and 5-HTergic transmission, as well as inhibiting the release of pro-inflammatory factor. Part Two: The antidepressant effect of aspirin in CCWS and its mechanisms. Aspirin improved the lower saccharin preference index in stressed rats depending on dosage, and increased the horizontal distance traveled in open field. Aspirin in high dose reduced both the retention time and the number of entries in open arms in EPM in stressed rats, but not controls. These data demonstrated that aspirin can ameliorate the depression-like behaviors induced by CCWS, while may increase anxiety level of stressed rats in high dose. However, CCWS had no significant effects on the level of monoamines, corticosterone and pro-inflammatory cytokines (IL-6 and TNF-α). In addition, there was no obvious dose-response relationship between aspirin doses and the level of monoamines, corticosterone and pro-inflammatory cytokines in stressed rats. In summary, aspirin can ameliorate the depression-like behaviors induced both by FST and CCWS. But the brain monoamines and the pro-inflammatory cytokines might be involved in the antidepressant effect of aspirin in FST, while their roles in depression-like behaviors induced by CCWS remain unknow, as they were not significantly affected by CCWS.
学科领域医学心理学
语种中文
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/20270
专题健康与遗传心理学研究室
作者单位中国科学院心理研究所
推荐引用方式
GB/T 7714
管西婷. 阿司匹林对应激诱导的抑郁样行为及神经生化、内分泌和免疫系统的影响[D]. 北京. 中国科学院研究生院,2011.
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