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脑内催产素:对未孕、妊娠和哺乳期大鼠神经内分泌应激反应及焦虑相关行为的差异性抑制

Brain oxytocin: differential inhibition of neuroendocrine stress responses and anxiety-related behaviour in virgin, pregnant and lactating rats.

作者信息

Neumann I D, Torner L, Wigger A

机构信息

Max Planck Institute of Psychiatry, Munich, Germany.

出版信息

Neuroscience. 2000;95(2):567-75. doi: 10.1016/s0306-4522(99)00433-9.

DOI:10.1016/s0306-4522(99)00433-9
PMID:10658637
Abstract

The involvement of brain oxytocin in the attenuated responsiveness of the hypothalamo-pituitary-adrenal axis and the oxytocin systems to external stressors found in pregnant and lactating rats has been studied, including both neuroendocrine and behavioural aspects. Intracerebroventricular infusion of an oxytocin receptor antagonist (0.75 microg/5 microl), but not of vehicle, elevated basal corticotropin and corticosterone secretion into blood of virgin female, but not of late pregnant or lactating rats. Oxytocin antagonist treatment further elevated the stress-induced (exposure to the elevated plus-maze or forced swimming) secretion of both corticotropin and corticosterone, but only in virgin and not in pregnant or lactating rats. Thus, corticotropin and corticosterone plasma concentrations remained attenuated in antagonist-treated pregnant and lactating animals. In contrast, infusion of the oxytocin antagonist significantly elevated the stress-induced secretion of oxytocin into blood in pregnant and lactating, but not in virgin, animals, indicating an autoinhibitory influence of intracerebral oxytocin on neurohypophysial oxytocin secretion induced by non-reproduction-related stimuli. Treatment with oxytocin antagonist 10 min prior to behavioural testing on the elevated plus-maze significantly reduced the anxiety-related behaviour in both pregnant and lactating rats, without exerting similar effects in virgin female rats. The results demonstrate a tonic inhibitory effect of endogenous oxytocin on corticotropin and, consequently, corticosterone secretion in virgin female rats, an effect which is absent in the peripartum period. In contrast, an anxiolytic action of endogenous oxytocin was detectable exclusively in pregnant and lactating rats. Therefore, we conclude that the actions of intracerebral oxytocin include independent effects on the responses of the hypothalamo-pituitary-adrenal axis and oxytocin systems to stressors and the anxiety-related behaviour which are modulated by the reproductive state of the animals.

摘要

已对大脑催产素在怀孕和哺乳期大鼠下丘脑 - 垂体 - 肾上腺轴及催产素系统对外部应激源反应减弱中的作用进行了研究,涵盖神经内分泌和行为两个方面。向脑室内注入催产素受体拮抗剂(0.75微克/5微升)而非赋形剂,可使未孕雌性大鼠血液中基础促肾上腺皮质激素和皮质酮分泌升高,但对妊娠后期或哺乳期大鼠无此作用。催产素拮抗剂处理进一步提高了应激诱导的(暴露于高架十字迷宫或强迫游泳)促肾上腺皮质激素和皮质酮分泌,但仅在未孕大鼠中出现,而在怀孕或哺乳期大鼠中未出现。因此,在接受拮抗剂处理的怀孕和哺乳期动物中,促肾上腺皮质激素和皮质酮的血浆浓度仍保持减弱状态。相比之下,向怀孕和哺乳期动物而非未孕动物脑室内注入催产素拮抗剂,可显著提高应激诱导的血液中催产素分泌,这表明脑内催产素对非生殖相关刺激诱导的神经垂体催产素分泌具有自抑制作用。在高架十字迷宫行为测试前10分钟用催产素拮抗剂处理,可显著降低怀孕和哺乳期大鼠的焦虑相关行为,而对未孕雌性大鼠无类似作用。结果表明,内源性催产素对未孕雌性大鼠的促肾上腺皮质激素进而对皮质酮分泌具有紧张性抑制作用,而在围产期不存在这种作用。相反,内源性催产素的抗焦虑作用仅在怀孕和哺乳期大鼠中可检测到。因此,我们得出结论,脑内催产素的作用包括对下丘脑 - 垂体 - 肾上腺轴及催产素系统对应激源的反应和焦虑相关行为具有独立影响,且这些影响受动物生殖状态的调节。

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