Hansson Caroline, Alvarez-Crespo Mayte, Taube Magdalena, Skibicka Karolina P, Schmidt Linnéa, Karlsson-Lindahl Linda, Egecioglu Emil, Nissbrandt Hans, Dickson Suzanne L
Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Neuropharmacology. 2014 Apr;79:498-505. doi: 10.1016/j.neuropharm.2013.12.012. Epub 2013 Dec 24.
The central ghrelin signaling system engages key pathways of importance for feeding control, recently shown to include those engaged in anxiety-like behavior in rodents. Here we sought to determine whether ghrelin impacts on the central serotonin system, which has an important role in anxiety. We focused on two brain areas, the amygdala (of importance for the mediation of fear and anxiety) and the dorsal raphe (i.e. the site of origin of major afferent serotonin pathways, including those that project to the amygdala). In these brain areas, we measured serotonergic turnover (using HPLC) and the mRNA expression of a number of serotonin-related genes (using real-time PCR). We found that acute central administration of ghrelin to mice increased the serotonergic turnover in the amygdala. It also increased the mRNA expression of a number of serotonin receptors, both in the amygdala and in the dorsal raphe. Studies in ghrelin receptor (GHS-R1A) knock-out mice showed a decreased mRNA expression of serotonergic receptors in both the amygdala and the dorsal raphe, relative to their wild-type littermates. We conclude that the central serotonin system is a target for ghrelin, providing a candidate neurochemical substrate of importance for ghrelin's effects on mood.
中枢胃饥饿素信号系统参与了对进食控制至关重要的关键途径，最近研究表明这些途径包括啮齿动物中与焦虑样行为相关的途径。在此，我们试图确定胃饥饿素是否会影响在焦虑中起重要作用的中枢5-羟色胺系统。我们聚焦于两个脑区，杏仁核（对恐惧和焦虑的调节很重要）和中缝背核（即主要5-羟色胺传入通路的起源部位，包括那些投射到杏仁核的通路）。在这些脑区，我们测量了5-羟色胺能代谢（使用高效液相色谱法）以及一些与5-羟色胺相关基因的mRNA表达（使用实时聚合酶链反应）。我们发现，对小鼠进行胃饥饿素的急性中枢给药会增加杏仁核中的5-羟色胺能代谢。它还会增加杏仁核和中缝背核中一些5-羟色胺受体的mRNA表达。对胃饥饿素受体（GHS-R1A）基因敲除小鼠的研究表明，相对于它们的野生型同窝小鼠，杏仁核和中缝背核中5-羟色胺能受体的mRNA表达均降低。我们得出结论，中枢5-羟色胺系统是胃饥饿素的作用靶点，为胃饥饿素对情绪的影响提供了一种重要的候选神经化学底物。
