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青少期应激对成年大鼠抑郁样行为和脑单胺类递质的影响及抗抑郁药物的作用
其他题名The effects of adolescent stress on emotional behaviors and brain monoamines in adult rats and the role of antidepressant
谢希
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
关键词青少期 慢性温和应激 抑郁样行为 焦虑样行为 单胺类神经递质
摘要临床流行病学调查表明,青少期负性生活事件导致个体成年后抑郁症、焦虑症等情绪疾病的易感性增加。青少期应激增加情绪疾病风险的发展神经生物学机制目前尚不清楚。通过不同类型应激(社会隔离VS 慢性温和应激)和发育阶段(青少期VS 成年期)大鼠的比较研究,本研究系统考察青少期应激对成年大鼠情绪行为和前额叶皮质及皮层下边缘脑区单胺能系统反应的影响,以及不同类型抗抑郁药物的治疗作用,建立青少期应激所致成年大鼠情绪障碍易感动物模型。研究采用糖水偏好测试(一种反映快感缺乏程度的指标)、开场和强迫游泳测试检测抑郁样行为;采用高架十字迷宫检测焦虑样行为;采用高效液相色谱法检测前额叶,海马,杏仁核和纹状体单胺能神经递质及其代谢物的水平。主要研究结果如下: 1. 青少期慢性温和应激(PND28-41)对成年大鼠(>PND62)的糖水偏好指数和旷场自发活动性没有影响,但在强迫游泳测试中表现出更多的绝望行为(不动行为增加)和更少的主动行为(挣扎行为减少)。此外,青少期慢性温和应激增加成年大鼠高架十字迷宫中的焦虑样行为。 2. 青少期慢性温和应激导致大鼠成年后纹状体5-HT 代谢率(5-HIAA/5-HT)和杏仁核DA 含量升高,而海马5-HT 代谢率降低。进一步的相关分析显示,青少期应激导致的大鼠挣扎行为和不动行为变化分别与纹状体5-HIAA/5-HT 呈负相关和正相关。 3. 5-羟色胺再摄取抑制剂氟西汀和多巴胺再摄取抑制剂安非他酮都能减少强迫游泳测试的不动行为,同时分别增加游动行为和挣扎行为。但与对照组相比,氟西汀对应激组大鼠强迫游泳测试中行为的改善作用减弱。神经生化检测结果表明,氟西汀能够逆转应激导致的纹状体5-HT 代谢率增加,安非他酮可以逆转应激造成的大鼠杏仁核DA 增加。综上所述,青少期慢性温和应激并不影响大鼠成年后偏好糖水的本能行为,但导致其应激应对能力受损,对成年应激事件更容易发展出次级的应对无能或绝望的抑郁样行为;同时青少期慢性温和应激导致成年大鼠海马,杏仁核和纹状体多巴胺和5-羟色胺及其代谢物含量持续改变。抗抑郁药物氟西汀和安非他酮都能够改善应激诱导的抑郁样行为改变,该治疗作用可能分别通过逆转应激导致的纹状体5-HT 代谢率和杏仁核DA 改变所介导。 这些结果从表面效度,结构效度和预测效度三个方面表明青少期慢性温和应激可以作为成年大鼠应激性抑郁易感动物模型。
其他摘要Epidemiological studies showed that the negative life events in adolescence increased the individual susceptibility to mood disorders, such as depression and anxiety. However, the developmental neurobiological mechanisms by which adolescent stress leads to psychopathology remain unknown. In this study, we examined the long-term effects of different stress paradigms (social isolation versus chronic mild stress) delivered at different development stage (adolescence versus adulthood) on emotional behaviors and monoamines in prefrontal cortex and subcortical limbic,areas, as well as the treatment efficacy of antidepressants. Depression-like behaviors were detected by sucrose preference test (an index of anhedonia), open field (OF) test and forced swimming test (FST), while anxiety-like behaviors were tested in elevated plus-maze (EPM). A high performance liquid chromatographic method was used to determine the level of monoamines and their metabolites in prefrontal, hippocampus, amygdala and striatum. The results were as follows: 1. Chronic mild stress in adolescence (PND28-41) had no effects on sucrose preferences and locomotion activity of adult rats (> PND62). But previously stressed rats exhibited an increased immobility/despair behavior and decreased climbing behavior in FST. In addition, the adult rats suffering stress during adolescence showed increased anxiety-like behavior in EPM. 2. Chronic mild stress in adolescence affected adult monoamines and metablites levels in several limbic regions, causing increased 5-HT turnover rate (5-HIAA/5-HT) in striatum and DA content in amygdale, and decreased 5-HIAA/5-HT in hippocampus.Moreover, the number of climbing behavior and immobility behavior in FST respectively had a negative and positive correlation with 5-HIAA/5-HT in striatum. 3. Both 5 - HT reuptake inhibitors fluoxetine and dopamine reuptake inhibitor bupropion can reduce immobility behavior, and increased swimming behavior and climbing behavior in FST respectively. However, flunexine exerted greater behavioral effects in FST in controls than stressed rats. In addition, fluoxetine can reverse the increase of 5-HIAA/5-HT in the striatum induced by adolescent stress, while bupropion can reverse the increase of DA level in amygdale induced by adolescent stress. In summary, chronic mild stress during adolescentce did not affect the instinct preference for sucrose of adult rats, but impaired behaviors implicated in motivation and stress coping. Rats exposure to adolescent chronic mild stress developed more significant despair behaviors after acute severe stress in adulthood. In addition, the long-term effects of chronic mild stress during adolescence on behavior draw a parallel with changes in 5-HT turnover rate in striatum and DA content in amygdale, all of that can be reversed by antidepressant fluoxetine and bupropion treatment respectively. These results suggested that the “adolescent chronic mild stress” model might be relevant to reported predisposition to develop depressive behaviors following stress in adulthood. 
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/311026/20423
专题健康与遗传心理学研究室
推荐引用方式
GB/T 7714
谢希. 青少期应激对成年大鼠抑郁样行为和脑单胺类递质的影响及抗抑郁药物的作用[D]. 北京. 中国科学院研究生院,2011.
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