Nisbett Khalin E, Koob George F
Graduate Program in Neuroscience, Graduate College, University of Illinois Chicago, Chicago, IL 60607, USA.
Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
eNeuro. 2025 Aug 8. doi: 10.1523/ENEURO.0059-25.2025.
Given the observed interaction and reports of oxytocin, μ-opioid receptor, or κ-opioid receptor expression in brain regions important to emotion regulation (i.e., the central amygdala), we hypothesized that oxytocin (), μ-opioid (), and κ-opioid () receptor mRNA were colocalized to the same cells in the central amygdala. RNAScope in situ hybridization using fresh frozen coronal brain sections was used to label cells containing , , and/or The coronal sections were imaged using a 40X objective (widefield fluorescence) on a Leica Thunder Fluorescent Microscope and the images were processed using open-source ImageJ/Fiji software and analyzed using Imaris software. The central amygdala was identified using Paxinos and Watson's The Mouse Brain in Stereotaxic Coordinates (Paxinos and Franklin 2019). Eight distinct cell populations were enumerated; i.e., only, only, only, + only, + only, + only, + + , and non-transcript cells. Our findings demonstrated that 47% of cells in the central amygdala express with and/or Of the -expressing cells, 38% colocalized only and 56% of -expressing cells colocalized both and Whereas 53% of -expressing cells colocalize and 61% of -expressiong cells colocalize These findings suggest that opioid and oxytocin receptors can function at the cellular level through morphological interactions. Future work will examine the physiological basis for the interaction between opioid and oxytocin receptors using transgenic behavior and electrophysiological assays. We report novel findings that a large proportion of central amygdala cells co-express and receptor mRNA, and a substantial proportion of central amygdala cells co-express , , and These data are significant and support our hypothesis of an interaction between opioid and oxytocin receptors, an interaction that has not yet been explored in the central nervous system. These findings underscore the unique and intricate role of opioids in regulating oxytocinergic systems, providing valuable insights into their therapeutic implications for anxiety disorders. This interaction is particularly interesting considering that both systems may have efficacy in mitigating some neuroadaptations that are associated with substance use disorders, particularly alcohol misuse and alcohol use disorder, which are often comorbid with anxiety.
鉴于在对情绪调节至关重要的脑区（即中央杏仁核）中观察到的催产素、μ-阿片受体或κ-阿片受体表达的相互作用及相关报道，我们推测催产素（）、μ-阿片（）和κ-阿片（）受体mRNA在中央杏仁核的同一细胞中共定位。使用新鲜冷冻冠状脑切片的RNAscope原位杂交技术来标记含有、和/或的细胞。在徕卡Thunder荧光显微镜上使用40X物镜（宽视野荧光）对冠状切片进行成像，并使用开源的ImageJ/Fiji软件处理图像，再使用Imaris软件进行分析。利用帕西诺斯和沃森的《立体定位坐标中的小鼠脑图谱》（帕西诺斯和富兰克林，2019年）来识别中央杏仁核。统计了八个不同的细胞群体，即仅表达、仅表达、仅表达、仅表达 + 、仅表达 + 、仅表达 + 、表达 + + 以及不表达转录本的细胞。我们的研究结果表明，中央杏仁核中47%的细胞表达，并与和/或共定位。在表达的细胞中，38%仅与共定位，56%的表达细胞同时与和共定位。而53%的表达细胞与共定位，61%的表达细胞与共定位。这些发现表明阿片受体和催产素受体可通过形态学相互作用在细胞水平发挥作用。未来的工作将使用转基因行为和电生理检测来研究阿片受体与催产素受体相互作用的生理基础。我们报告了新的发现，即很大比例的中央杏仁核细胞共表达和受体mRNA，并且相当比例的中央杏仁核细胞共表达、和。这些数据意义重大，支持了我们关于阿片受体与催产素受体相互作用的假设，这种相互作用在中枢神经系统中尚未得到探索。这些发现强调了阿片类物质在调节催产素能系统中的独特而复杂的作用，为它们对焦虑症的治疗意义提供了有价值的见解。考虑到这两个系统可能在减轻一些与物质使用障碍相关的神经适应性变化方面都有功效，这种相互作用尤其有趣，特别是酒精滥用和酒精使用障碍，它们常常与焦虑症共病。
