5-羟色胺及其突触后1A受体对慢性应激大鼠情绪和认知的影响

目的:研究5-羟色胺(5-HT)及其突触后1A受体(5-HT1A)在应激适应中的作用.方法:使用对氯苯丙胺(p-PCA)将大鼠体内5-HT耗竭,并使用5-HT1A受体激动剂8-OH-DPAT及拮抗荆WAY100635,研究慢性应激、5-HT及其突触后5-HT1A受体等对大鼠在高架十字迷宫、强迫游泳和水迷宫测试中行为的影响.结果:应激后5-HT耗竭大鼠比正常大鼠在高架十字迷宫实验中开臂停留时间较少,闭臂停留时间较多;强迫游泳实验中不动时间较长;在水迷宫测试的第3,4天,逃离潜伏期明显增加,测试时在目标象限停留时间和穿越原平台位置次数明显减少.8-OH-DPAT能显著减少5-HT耗竭大鼠及5-HT耗竭应激大鼠焦虑和抑郁水平,上述作用则能被WAY100635阻断.在水迷宫实验中,8-OH-DPAT及WAY100635对大鼠找到平台的平均潜伏期、在目标象限的时间和穿越平台的次数无明显影响.结论:5-HT耗竭大鼠应激时更容易产生抑郁和焦虑症状,并易导致学习、记忆等认知功能受损,时应激适应能力下降.突触后5-HT1A的激活能够缓解5-HT耗竭及5-HT耗竭应激大鼠的焦虑和抑郁症状,促进对慢性应激的适应,但其对大鼠的学习记忆等认知功能无明显影响.

Effect of 5-HT and postsynaptic 5-HT1A on the mood and recogniztion of the repeated restraint stress in rats

OBJECTIVE: To explore the role of 5-HT and postsynaptic 5-HT1A receptors in the stress adaptation. METHODS: p-PCA was used to deplete the 5-HT in rats. The 5-HT1A agonist 8-OH-DPAT and antagonist WAY100635 were used to determine the effect of postsynaptic 5-HT1A receptors on the ratso behaviors in the Elevated Plus-Maze test, the Forced Swimming test, and the Morris Water Maze test. RESULTS: Compared with the intact rats, the 5-HT depleted rats showed more seriously anxious behaviors in the Elevated Plus-Maze test and more obvious learned helplessness in the Forced Swimming test. After having been stressed the 5-HT depleted rats showed significantly impaired learning and memory compared with the intact rats according to Morris Water Maze test. Activation of postsynaptic 5-HT1A receptors by 8-OH-DPAT in the 5-HT depleted rats or the 5-HT depleted stress rats significantly decreased the symptoms of anxiety and learned helplessness behaviors which were prevented by the treatment of WAY100635. The 8-OH-DPAT and WAY100635 had no obvious effect on the 5-HT depletion or 5-HT depleted stress rats in the Morris Water Maze test. CONCLUSION: Deficiency of 5-HT in rats may suppress its ability to stress adaptation. Activation of post-synaptic 5-HT1A receptors can attenuate the anxiety and depressive behavior symptoms, and facilitate rats to adapt stress.