Department of Psychology & Neuroscience, The University of North Carolina, Chapel Hill, NC, 27599-3270, USA.
Bowles Center for Alcohol Studies, The University of North Carolina, Chapel Hill, NC, 27599-7178, USA.
Neuropsychopharmacology. 2024 Mar;49(4):690-698. doi: 10.1038/s41386-023-01742-w. Epub 2023 Sep 27.
Neuropeptide Y (NPY) signaling regulation of corticolimbic communication is known to modulate binge-like ethanol consumption in rodents. In this work we sought to assess the impact of intra-BLA NPY system modulation on binge-like ethanol intake and to assess the role of the NPY1R+ projection from the BLA to the mPFC in this behavior. We used "drinking-in-the-dark" (DID) procedures in C57BL6J mice to address these questions. First, the impact of intra-BLA administration of NPY on binge-like ethanol intake was assessed. Next, the impact of repeated cycles of DID intake on NPY1R expression in the BLA was assessed with use of immunohistochemistry (IHC). Finally, chemogenetic inhibition of BLA→mPFC NPY1R+ projections was assessed to determine if limbic communication with the mPFC was specifically involved in binge-like ethanol intake. Importantly, as both the BLA and NPY system are sexually dimorphic, both sexes were assessed in these studies. Intra-BLA NPY dose-dependently decreased binge-like ethanol intake in males only. Repeated DID reduced NPY1R expression in the BLA of both sexes. Silencing of BLA→mPFC NPY1R+ neurons significantly reduced binge-like ethanol intake in both sexes in a dose-dependent manner. We provide novel evidence that (1) intra-BLA NPY reduces binge-like ethanol intake in males; (2) binge-like ethanol intake reduces NPY1R levels in the BLA; and (3) chemogenetic inhibition of BLA→mPFC NPY1R+ neurons blunts binge-like drinking in male and female mice. These observations provide the first direct evidence that NPY signaling in the BLA, and specifically BLA communication with the mPFC, modulates binge-like ethanol consumption.
神经肽 Y（NPY）信号调节皮质边缘通讯已知可调节啮齿动物的类似狂欢样乙醇消耗。在这项工作中，我们试图评估内侧眶额皮质（BLA）内 NPY 系统调节对类似狂欢样乙醇摄入的影响，并评估 BLA 到前额皮质（mPFC）的 NPY1R+投射在这种行为中的作用。我们使用 C57BL6J 小鼠的“暗饮”（DID）程序来解决这些问题。首先，评估了 BLA 内给予 NPY 对类似狂欢样乙醇摄入的影响。接下来，使用免疫组织化学（IHC）评估了重复 DID 摄入对 BLA 中 NPY1R 表达的影响。最后，评估了 BLA→mPFC NPY1R+投射的化学遗传抑制作用，以确定与 mPFC 的边缘通讯是否特别参与类似狂欢样乙醇摄入。重要的是，由于 BLA 和 NPY 系统都具有性别二态性，因此在这些研究中评估了两性。BLA 内 NPY 剂量依赖性地仅减少雄性的类似狂欢样乙醇摄入。重复 DID 减少了两性 BLA 中 NPY1R 的表达。BLA→mPFC NPY1R+神经元的沉默以剂量依赖性方式显著减少了两性的类似狂欢样乙醇摄入。我们提供了新的证据，表明（1）BLA 内 NPY 减少雄性的类似狂欢样乙醇摄入；（2）类似狂欢样乙醇摄入降低了 BLA 中的 NPY1R 水平；（3）BLA→mPFC NPY1R+神经元的化学遗传抑制减弱了雄性和雌性小鼠的类似狂欢样饮酒。这些观察结果提供了直接证据，表明 BLA 中的 NPY 信号传导，特别是 BLA 与 mPFC 的通讯，调节了类似狂欢样乙醇消耗。
