Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA; Department of Cell Biology & Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Alcohol. 2024 Nov;120:179-193. doi: 10.1016/j.alcohol.2024.06.005. Epub 2024 Jun 29.
While there are numerous brain regions that have been shown to play a role in this AUD in humans and animal models, the central nucleus of the amygdala (CeA) has emerged as a critically important locus mediating binge alcohol consumption. In this study, we sought to understand how relative gene expression of key signaling molecules in the CeA changes during different periods of abstinence following bouts of binge drinking. To test this, we performed drinking in the dark (DID) on two separate cohorts of C57BL/6J mice and collected CeA brain tissue at 1 day (acute) and 7 days (protracted) abstinence after DID. We used qRTPCR to evaluate relative gene expression changes of 25 distinct genes of interest related to G protein-coupled receptors (GPCRs), neuropeptides, ion channel subunits, and enzymes that have been previously implicated in AUD. Our findings show that during acute abstinence CeA punches collected from female mice had upregulated relative mRNA expression of the gamma-aminobutyric acid receptor subunit alpha 2 (Gabra2), and the peptidase, angiotensinase c (Prcp). CeA punches from male mice at the same time point in abstinence had upregulated relative mRNA encoding for neuropeptide-related molecules, neuropeptide Y (Npy) and somatostatin (Sst), as well as the neuropeptide Y receptor Y2 (Npyr2), but downregulated Glutamate ionotropic receptor NMDA type subunit 1 (Grin1). After protracted abstinence, CeA punches collected from female mice had increased mRNA expression of corticotropin releasing hormone (Crh) and Npy. CeA punches collected from male mice at the same timepoint had upregulated relative mRNA expression of Npy2r, Npy, and Sst. Our findings support that there are differences in how the CeA of male and female mice respond to binge-alcohol exposure, highlighting the need to understand the implications of such differences in the context of AUD and binge drinking behavior.
虽然已经有许多大脑区域被证明在人类和动物模型中的酒精使用障碍（AUD）中发挥作用，但杏仁中央核（CeA）已成为介导 binge 饮酒的关键重要中枢。在这项研究中，我们试图了解 CeA 中的关键信号分子的相对基因表达在 binge 饮酒后的不同禁欲期如何变化。为此，我们对两组 C57BL/6J 小鼠进行了暗饮（DID），并在 DID 后 1 天（急性）和 7 天（迁延）禁欲时收集 CeA 脑组织。我们使用 qRT-PCR 评估了与 G 蛋白偶联受体（GPCR）、神经肽、离子通道亚基和先前与 AUD 相关的酶相关的 25 个感兴趣的基因的相对基因表达变化。我们的研究结果表明，在急性禁欲期间，从雌性小鼠中收集的 CeA 打孔组织中，γ-氨基丁酸受体亚基 alpha 2（Gabra2）和肽酶血管紧张素酶 C（Prcp）的相对 mRNA 表达上调。处于相同禁欲时间点的雄性小鼠的 CeA 打孔组织中，与神经肽相关的分子神经肽 Y（Npy）和生长抑素（Sst）以及神经肽 Y 受体 Y2（Npyr2）的编码相对 mRNA 上调，但谷氨酸离子型受体 NMDA 型亚基 1（Grin1）下调。在迁延禁欲后，从雌性小鼠中收集的 CeA 打孔组织中促肾上腺皮质激素释放激素（Crh）和 Npy 的 mRNA 表达增加。在同一时间点从雄性小鼠中收集的 CeA 打孔组织中，Npy2r、Npy 和 Sst 的相对 mRNA 表达上调。我们的研究结果支持雄性和雌性小鼠的 CeA 对 binge 酒精暴露的反应存在差异，这突出表明需要了解 AUD 和 binge 饮酒行为背景下这种差异的含义。
