Arendt David H, Ronan Patrick J, Oliver Kevin D, Callahan Leah B, Summers Tangi R, Summers Cliff H
Department of Biology, University of South Dakota, Vermillion, SD 57069-2390, USA.
Behav Neurosci. 2013 Feb;127(1):86-94. doi: 10.1037/a0031442.
The orexin/hypocretin peptide signaling system plays a neuromodulatory role in motivation and stress; two critical components of depression. Although work has been done to identify links between orexin and depression, few specific neuroanatomical associations have been made. These studies have not investigated the relationship between orexin and orexin receptor expression in specific brain regions associated with this disorder. To address this, we examined immobility during the forced swim test (FST) in mice, a commonly used measure of depressive behavior. We analyzed the variation in FST immobility with the distribution of orexin and its receptor mRNA. We found that animals that exhibited more robust depressive behavior had greater or lesser orexin system expression that depended on the limbic brain region analyzed. In the hippocampus there was a negative correlation between orexin expression and FST immobility. Animals that displayed relatively more depressive behavior had lower hippocampal expression of Orexin A (OrxA). In the amygdala, there was a curvilinear relationship between OrxA and FST performance. In addition there was a positive correlation with amygdalar Type I orexin receptor (Orx1) mRNA and depressive behavior. Despite the differences in limbic orexin expression, there was no correlation between immobility and hypothalamic orexin neuron activation as measured by c-Fos. Overall, more severe depressive behavior was associated with reduced hippocampal orexin expression, contrasted with increased orexin plus Orx1 receptor mRNA expression in the amygdala. This divergent pattern between the hippocampus and amygdala mirrors a neurobiological theme seen in depression resulting from reduced hippocampal, but increased amygdalar, size and function.
食欲素/下丘脑泌素肽信号系统在动机和应激（抑郁症的两个关键组成部分）中发挥神经调节作用。尽管已经开展了一些工作来确定食欲素与抑郁症之间的联系，但几乎没有建立具体的神经解剖学关联。这些研究尚未调查食欲素与其在与该疾病相关的特定脑区中的受体表达之间的关系。为了解决这个问题，我们检测了小鼠在强迫游泳试验（FST）中的不动时间，这是一种常用的抑郁行为测量方法。我们分析了FST不动时间的变化与食欲素及其受体mRNA分布之间的关系。我们发现，表现出更强抑郁行为的动物，其食欲素系统表达的增减取决于所分析的边缘脑区。在海马体中，食欲素表达与FST不动时间呈负相关。表现出相对更多抑郁行为的动物，其海马体中食欲素A（OrxA）的表达较低。在杏仁核中，OrxA与FST表现之间存在曲线关系。此外，杏仁核I型食欲素受体（Orx1）mRNA与抑郁行为呈正相关。尽管边缘食欲素表达存在差异，但通过c-Fos测量的不动时间与下丘脑食欲素神经元激活之间没有相关性。总体而言，更严重的抑郁行为与海马体食欲素表达降低相关，与之形成对比的是，杏仁核中食欲素加Orx1受体mRNA表达增加。海马体和杏仁核之间的这种不同模式反映了抑郁症中一个神经生物学特征，即海马体体积和功能减小，但杏仁核体积和功能增大。
