期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：48
页码：13893-13898
DOI：10.1073/pnas.1616664113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceSodium appetite is an important instinctive behavior with high survival value. Although a role of opioid signaling in salt appetite has been identified in rats, the exact contribution made by different opioid receptor subtypes within specific brain regions is not fully characterized. Here, we report that mu-opioid receptor (MOR) signaling is intrinsically responsible for opioid-dependent sodium appetite rendered by sodium deficiency in mice. Furthermore, we identified that during gratification of sodium appetite, the central amygdala is activated, and endogenous MOR signaling within this region promotes sodium intake in sodium-depleted mice. Accordingly, we reveal a key nucleus within the endogenous opioid circuit that is likely to be conserved across mammals and important in the control of dietary sodium consumption. Due to the importance of dietary sodium and its paucity within many inland environments, terrestrial animals have evolved an instinctive sodium appetite that is commensurate with sodium deficiency. Despite a well-established role for central opioid signaling in sodium appetite, the endogenous influence of specific opioid receptor subtypes within distinct brain regions remains to be elucidated. Using selective pharmacological antagonists of opioid receptor subtypes, we reveal that endogenous mu-opioid receptor (MOR) signaling strongly drives sodium appetite in sodium-depleted mice, whereas a role for kappa (KOR) and delta (DOR) opioid receptor signaling was not detected, at least in sodium-depleted mice. Fos immunohistochemistry revealed discrete regions of the mouse brain displaying an increased number of activated neurons during sodium gratification: the rostral portion of the nucleus of the solitary tract (rNTS), the lateral parabrachial nucleus (LPB), and the central amygdala (CeA). The CeA was subsequently targeted with bilateral infusions of the MOR antagonist naloxonazine, which significantly reduced sodium appetite in mice. The CeA is therefore identified as a key node in the circuit that contributes to sodium appetite. Moreover, endogenous opioids, acting via MOR, within the CeA promote this form of appetitive behavior.
关键词：sodium appetite ; mu-opioid receptor ; central amygdala
