Abstract
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.
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Funding
The authors thank Rhiannon D. Thomas for her technical assistance and Richard Palmiter, PhD for supplying the NPY1R-cre mice. This work was supported by National Institutes of Health grants AA022048, AA013573, AA015148, and F32AA025811. The authors declare no competing interests.
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Robinson, S.L., Marrero, I.M., Perez-Heydrich, C.A. et al. Medial prefrontal cortex neuropeptide Y modulates binge-like ethanol consumption in C57BL/6J mice. Neuropsychopharmacol. 44, 1132–1140 (2019). https://doi.org/10.1038/s41386-018-0310-7
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DOI: https://doi.org/10.1038/s41386-018-0310-7
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