Wotjak C T, Kubota M, Liebsch G, Montkowski A, Holsboer F, Neumann I, Landgraf R
Max Planck Institute of Psychiatry, Munich, Germany.
J Neurosci. 1996 Dec 1;16(23):7725-32. doi: 10.1523/JNEUROSCI.16-23-07725.1996.
The effects of emotional stressors on the release of arginine vasopressin (AVP) and oxytocin (OXT) within the rat hypothalamus and the origin and physiological significance of AVP released within the hypothalamic paraventricular nucleus (PVN) were investigated. First, adult male Wistar rats with a microdialysis probe aimed at the PVN or the supraoptic nucleus were exposed to either a dominant male rat (social defeat) or a novel cage. Release of AVP within the PVN was significantly increased in response to social defeat but not to novelty. In contrast to an activation of the hypothalamic-pituitary-adrenal (HPA) system, neither stressor stimulated the hypothalamic-neurohypophysial system (unchanged plasma AVP and OXT and unchanged release within the supraoptic nucleus [AVP] and the PVN [OXT]). Next, we demonstrated by simultaneous microdialysis of the suprachiasmatic nucleus and the PVN that AVP measured in PVN dialysates during social defeat was probably of intranuclear origin. Finally, a mixture of a V1 AVP and the alpha-helical corticotropin-releasing hormone (CRH) receptor antagonists administered via inverse microdialysis into the PVN caused a significant increase in the plasma adrenocorticotropic hormone (ACTH) concentration compared with vehicle-treated controls both under basal conditions and during social defeat, indicating inhibitory effects of intra-PVN-released AVP and/or CRH on HPA system activity. The antagonists failed to affect anxiety-related behavior of the animals as assessed with the elevated plus-maze. Taken together, our results show for the first time that AVP is released within the PVN in response to an emotional stressor. We hypothesize that this intranuclear release provides a negative tonus on ACTH secretion.
研究了情绪应激源对大鼠下丘脑内精氨酸加压素（AVP）和催产素（OXT）释放的影响，以及下丘脑室旁核（PVN）内释放的AVP的来源和生理意义。首先，将微透析探针分别指向PVN或视上核的成年雄性Wistar大鼠暴露于优势雄性大鼠（社会挫败）或新笼子中。与新环境相比，社会挫败显著增加了PVN内AVP的释放。与下丘脑-垂体-肾上腺（HPA）系统的激活不同，两种应激源均未刺激下丘脑-神经垂体系统（血浆AVP和OXT不变，视上核[AVP]和PVN[OXT]内的释放也不变）。接下来，我们通过对视交叉上核和PVN同时进行微透析证明，社会挫败期间PVN透析液中测得的AVP可能起源于核内。最后，通过反向微透析将V1 AVP和α-螺旋促肾上腺皮质激素释放激素（CRH）受体拮抗剂混合物注入PVN，结果显示，与基础条件下和社会挫败期间的溶剂处理对照组相比，血浆促肾上腺皮质激素（ACTH）浓度显著升高，这表明PVN内释放的AVP和/或CRH对HPA系统活性具有抑制作用。用高架十字迷宫评估发现，拮抗剂未能影响动物的焦虑相关行为。综上所述，我们的结果首次表明，情绪应激源可促使PVN内释放AVP。我们推测，这种核内释放对ACTH分泌起到负性调节作用。
