Neumann I D, Krömer S A, Toschi N, Ebner K
Max Planck Institute of Psychiatry, Kraepelinstr. 2, D80804, Munich, Germany.
Regul Pept. 2000 Dec 22;96(1-2):31-8. doi: 10.1016/s0167-0115(00)00197-x.
In response to various stressors, oxytocin is released not only into blood, but also within hypothalamic and extrahypothalamic limbic brain regions. Here, we describe the involvement of intracerebrally released oxytocin in the regulation of the activity of the hypothalamo-pituitary-adrenal (HPA) axis by infusion of the oxytocin receptor antagonist (des Gly-NH(2) d(CH(2))(5) [Tyr(Me)(2), Thr(4)] OVT; pH 7.4; Dr. M. Manning, Toledo, OH, USA) either into the lateral cerebral ventricle (icv[0.75 microg/5 microl,]) or via retrodialysis (10 microg/ml, 3.3 microl/min, 15 min) into the hypothalamic paraventricular nuclei (PVN), the medio-lateral septum or the amygdala. Male Wistar rats fitted with a chronic jugular vein catheter and an icv guide cannula or a microdialysis probe targeting the respective brain region 4 days prior to the experiment were blood sampled under basal as well as stressful conditions. Rats were exposed to the elevated platform (emotional stressor) and/or to forced swimming (combined physical and emotional stressor). Blockade of the receptor-mediated action of endogenous oxytocin within the PVN resulted in an enhanced basal secretion of ACTH whereas, in response to forced swimming, ACTH secretion was rather reduced, indicating a tonic inhibitory effect of OXT on basal HPA axis activity, but a potentiating action under conditions of stress. Within the medio-lateral septum, antagonist treatment did not alter basal ACTH secretion, but significantly disinhibited ACTH secretion in response to the elevated platform, but not to forced swimming. Within the amygdala, no significant effects either on basal or stress-induced HPA axis activity could be found. The results indicate a differential involvement of brain oxytocin in the regulation of the HPA axis activity which depends both on the site of intracerebral oxytocin release and the stressor the animals are exposed to.
作为对各种应激源的反应,催产素不仅会释放到血液中,还会释放到下丘脑和下丘脑外边缘脑区。在此,我们通过向侧脑室(脑室内注射[0.75微克/5微升])或通过逆向透析(10微克/毫升,3.3微升/分钟,15分钟)向下丘脑室旁核(PVN)、中隔外侧或杏仁核注入催产素受体拮抗剂(去甘氨酰胺 - d(CH₂)₅ [酪氨酸(甲基)₂,苏氨酸⁴] 催产素;pH 7.4;美国俄亥俄州托莱多市的M. Manning博士),来描述脑内释放的催产素在调节下丘脑 - 垂体 - 肾上腺(HPA)轴活性中的作用。在实验前4天,给雄性Wistar大鼠安装慢性颈静脉导管和针对相应脑区的脑室内引导套管或微透析探针,在基础和应激条件下采集血液样本。大鼠暴露于高架平台(情绪应激源)和/或强迫游泳(身体和情绪联合应激源)。阻断PVN内内源性催产素的受体介导作用会导致促肾上腺皮质激素(ACTH)基础分泌增加,而在强迫游泳时,ACTH分泌反而减少,这表明催产素对基础HPA轴活性具有紧张性抑制作用,但在应激条件下具有增强作用。在中隔外侧,拮抗剂处理未改变基础ACTH分泌,但在高架平台刺激下显著解除了对ACTH分泌的抑制,而对强迫游泳无此作用。在杏仁核内,无论是基础还是应激诱导的HPA轴活性均未发现显著影响。结果表明,脑内催产素在调节HPA轴活性中的作用存在差异,这既取决于脑内催产素释放的部位,也取决于动物所暴露的应激源。