Medial prefrontal cortex neuropeptide Y modulates binge-like ethanol consumption in C57BL/6J mice.,Neuropsychopharmacology

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Medial prefrontal cortex neuropeptide Y modulates binge-like ethanol consumption in C57BL/6J mice.
Neuropsychopharmacology ( IF 6.6 ) Pub Date : 2019-01-07 , DOI: 10.1038/s41386-018-0310-7
Stacey L Robinson _{1,

2} , Isabel M Marrero ₁ , Carlos A Perez-Heydrich ₁ , Marian T Sepulveda-Orengo ₁ , Kathryn J Reissner ₁ , Todd E Thiele _{1,

2}

Affiliation

Neuropeptide Y (NPY) signaling via limbic NPY1 and 2 receptors (NPY1R and NPY2R, respectively) is known to modulate binge-like ethanol consumption in rodents. However, the role of NPY signaling in the medial prefrontal cortex (mPFC), which provides top-down modulation of the limbic system, is unknown. Here, we used "drinking-in-the-dark" (DID) procedures in C57BL/6J mice to address this gap in the literature. First, the impact of DID on NPY immunoreactivity (IR) was assessed in the mPFC. Next, the role of NPY1R and NPY2R signaling in the mPFC on ethanol consumption was evaluated through site-directed pharmacology. Chemogenetic inhibition of NPY1R+ neurons in the mPFC was performed to further evaluate the role of this population. To determine the potential role of NPY1R+ neurons projecting from the mPFC to the basolateral amygdala (BLA) this efferent population was selectively silenced. Three, 4-day cycles of DID reduced NPY IR in the mPFC. Intra-mPFC activation of NPY1R and antagonism of NPY2R resulted in decreased binge-like ethanol intake. Silencing of mPFC NPY1R+ neurons overall, and specifically NPY1R+ neurons projecting to the BLA, significantly reduced binge-like ethanol intake. We provide novel evidence that (1) binge-like ethanol intake reduces NPY levels in the mPFC; (2) activation of NPY1R or blockade of NPY2R reduces binge-like ethanol intake; and (3) chemogenetic inhibition of NPY1R+ neurons in the mPFC and NPY1R+ mPFC neurons projecting to the BLA blunts binge-like drinking. These observations provide the first direct evidence that NPY signaling in the mPFC modulates binge-like ethanol consumption.

中文翻译：

内侧前额叶皮层神经肽 Y 调节 C57BL/6J 小鼠的狂欢样乙醇消耗。

已知神经肽 Y (NPY) 信号通过边缘系统 NPY1 和 2 受体（分别为 NPY1R 和 NPY2R）调节啮齿类动物的狂欢样乙醇消耗。然而，NPY 信号在提供边缘系统自上而下调节的内侧前额叶皮层 (mPFC) 中的作用尚不清楚。在这里，我们在 C57BL/6J 小鼠中使用“在黑暗中饮酒”（DID）程序来解决文献中的这一差距。首先，在 mPFC 中评估了 DID 对 NPY 免疫反应性 (IR) 的影响。接下来，通过定点药理学评估了 NPY1R 和 NPY2R 信号在 mPFC 中对乙醇消耗的作用。对 mPFC 中的 NPY1R+ 神经元进行化学抑制以进一步评估该群体的作用。为了确定从 mPFC 投射到基底外侧杏仁核 (BLA) 的 NPY1R+ 神经元的潜在作用，该传出群体被选择性地沉默。三、4 天的 DID 周期降低了 mPFC 中的 NPY IR。NPY1R 的 mPFC 内激活和 NPY2R 的拮抗作用导致类似暴饮暴食的乙醇摄入量减少。整体沉默 mPFC NPY1R+ 神经元，特别是投射到 BLA 的 NPY1R+ 神经元，显着减少了类似暴饮暴食的乙醇摄入量。我们提供了新的证据，表明 (1) 类似暴饮暴食的乙醇摄入会降低 mPFC 中的 NPY 水平；(2) NPY1R 的激活或 NPY2R 的阻断减少了类似暴饮暴食的乙醇摄入；(3) mPFC 中 NPY1R+ 神经元的化学遗传学抑制和投射到 BLA 的 NPY1R+ mPFC 神经元抑制暴饮暴食。

更新日期：2019-01-26

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