Cumbers M R, Chung S T, Wakerley J B
Department of Anatomy, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.
Neuropeptides. 2007 Aug;41(4):217-26. doi: 10.1016/j.npep.2007.04.004. Epub 2007 Jun 12.
Oxytocin functions as both a neurohypophysial hormone and central neuromodulatory peptide, and has been implicated in reproductive behaviours, anxiety and reward, as well as facilitation of the neuroendocrine milk-ejection reflex. A potential substrate for oxytocin is the supramammillary nucleus (SuM), a structure that contains oxytocin binding sites and serves as an important relay within the limbic system. Hence, this study investigated the neuromodulatory role of oxytocin within the SuM. Firstly, the effect of oxytocin on neuronal firing within the SuM was studied, using in vitro brain slices from virgin female rats. Oxytocin (10(-6)M) excited approximately 50% of SuM neurones, and similar results were obtained with the selective oxytocin agonist, Thr(4) Gly(7) oxytocin (TGOT) (10(-6) and 10(-7)M). The remaining neurones were unaffected. The TGOT response was blocked by application of the oxytocin antagonist, [d(CH(2))51,Tyr(Me)(2),Thr(4),Orn(8),Tyr-NH29]-vasotocin. Repeat doses of TGOT caused diminution of the response, indicative of desensitisation. In the second series of experiments, immunocytochemical techniques were used to study the oxytocinergic innervation of the SuM. The supramammillary decussation was found to contain numerous oxytocinergic fibres, and some could be seen coursing ventrally to enter the SuM. Whereas, some were clearly "en passant" fibres innervating the neurohypophysis, others followed a more convoluted and branching course, and appeared to terminate within the nucleus. Finally, in vivo microinfusion studies investigated whether oxytocin injected into the SuM facilitated the milk-ejection reflex, a well known action of central oxytocin. Oxytocin microinfusion in the region of the SuM caused a pronounced facilitation of the reflex, contrasting with the much smaller effects of microinfusions made rostral or caudal to the nucleus. Collectively, these results strongly support a neuromodulatory role for oxytocin within the SuM. This could have important implications for understanding the diverse neuroendocrine and behavioural functions of central oxytocin, including its role in reward.
催产素兼具神经垂体激素和中枢神经调节肽的功能，与生殖行为、焦虑和奖赏有关，还能促进神经内分泌性射乳反射。催产素的一个潜在作用靶点是乳头体上核（SuM），该结构含有催产素结合位点，是边缘系统内的一个重要中继站。因此，本研究探讨了催产素在SuM内的神经调节作用。首先，利用未交配雌性大鼠的体外脑片，研究了催产素对SuM内神经元放电的影响。催产素（10⁻⁶M）使约50%的SuM神经元兴奋，选择性催产素激动剂苏氨酸⁴甘氨酸⁷催产素（TGOT）（10⁻⁶和10⁻⁷M）也得到了类似结果。其余神经元未受影响。催产素拮抗剂[d(CH₂)₅¹,酪氨酸(Me)₂,苏氨酸⁴,鸟氨酸⁸,酪氨酸-NH₂⁹]-血管催产素可阻断TGOT的反应。重复给予TGOT会导致反应减弱，表明出现了脱敏现象。在第二组实验中，采用免疫细胞化学技术研究了SuM的催产素能神经支配。发现乳头体上交叉含有大量催产素能纤维，有些纤维可看到向腹侧延伸进入SuM。虽然有些显然是支配神经垂体的“过路”纤维，但其他纤维走行更曲折且有分支，似乎在核内终止。最后，体内微量注射研究考察了注入SuM的催产素是否能促进射乳反射，这是中枢催产素的一个众所周知的作用。在SuM区域微量注射催产素可显著促进该反射，与在核的头侧或尾侧进行微量注射产生的较小效应形成对比。总的来说，这些结果有力地支持了催产素在SuM内具有神经调节作用。这对于理解中枢催产素的多种神经内分泌和行为功能，包括其在奖赏中的作用，可能具有重要意义。
