Department of Biological Sciences, University of Waikato, Hamilton, New Zealand.
Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN, USA.
Neuroscience. 2017 Dec 16;366:54-61. doi: 10.1016/j.neuroscience.2017.10.008. Epub 2017 Oct 14.
Oxytocin (OT) administration in the ventromedial hypothalamic nucleus (VMH) reduces chow intake. The nature of VMH OT's anorexigenic action remains unclear. Here we provide insight into neural mechanisms underlying VMH OT-driven anorexia by (a) identifying feeding-related brain sites activated by VMH OT injection; (b) measuring VMH OT receptor (OTr) mRNA changes in response to hunger and palatability; and (c) examining how VMH OT affects episodic sweet solution intake in sated and hungry rats.
We established effective doses of VMH OT in deprivation-induced and scheduled feeding and determined whether an OT antagonist blocks the effect. Then, OT (or antagonist) was injected in the VMH of sated rats given episodically sucrose and saccharin solutions. OT was also injected in hungry animals offered simultaneously chow and sugar water. Brain activation after VMH OT was determined by Fos immunoreactivity (IR). OTr expression was established with rtPCR after chow deprivation or saccharin exposure.
VMH OT decreased intake of chow and the effect was reversed by the antagonist, though the antagonist alone was not orexigenic. OT did not affect intakes of energy-dilute saccharin and sucrose solutions in sated or hungry rats. Fos IR was elevated in the VMH and energy balance-related paraventricular and arcuate nuclei, but not reward areas. VMH OTr expression was higher in hungry rats than in sated controls; saccharin intake had no effect.
OT acting in the VMH decreases intake driven by energy not by palatability, and it stimulates activity of hypothalamic sites controlling energy balance.
在下丘脑腹内侧核（VMH）中给予催产素（OT）可减少进食量。VMH OT 的厌食作用的性质尚不清楚。在这里，我们通过（a）确定VMH OT 注射激活的与进食相关的大脑部位；（b）测量饥饿和适口性对 VMH OT 受体（OTr）mRNA 变化的反应；以及（c）检查 VMH OT 如何影响饱食和饥饿大鼠的间歇性甜味溶液摄入，为 VMH OT 驱动的厌食提供了对神经机制的深入了解。
我们确定了 VMH OT 在剥夺诱导和计划进食中的有效剂量，并确定了 OT 拮抗剂是否可以阻断其作用。然后，在给予间歇性蔗糖和糖精溶液的饱食大鼠的 VMH 中注射 OT（或拮抗剂）。同时，在提供食物和糖水的饥饿动物的 VMH 中注射 OT。通过 Fos 免疫反应性（IR）确定 VMH OT 后的脑激活。用 rtPCR 建立了 chow 剥夺或 saccharin 暴露后的 OTr 表达。
VMH OT 减少了 chow 的摄入量，拮抗剂可逆转该作用，但拮抗剂本身不具有食欲刺激作用。OT 对饱食或饥饿大鼠的能量稀释糖精和蔗糖溶液的摄入量没有影响。Fos IR 在 VMH 以及与能量平衡相关的室旁核和弓状核中升高，但不在奖励区域中升高。与饱食对照组相比，饥饿大鼠的 VMH OTr 表达更高；saccharin 摄入量没有影响。
作用于 VMH 的 OT 减少了由能量驱动的而不是由适口性驱动的摄入量，并且它刺激了控制能量平衡的下丘脑部位的活性。
