Glucagon-like peptide 1 receptors in nucleus accumbens affect food intake.
Glucagon-like peptide 1 receptors in nucleus accumbens affect food intake.
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DOI：
10.1523/jneurosci.3262-11.2011
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发表时间：
2011-10-12
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影响因子：
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通讯作者：
Williams DL
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作者：
Dossat AM;Lilly N;Kay K;Williams DL
中枢高血糖素样多肽1受体(GLP-1R)刺激抑制摄食，后脑GLP-1神经元投射到许多与摄食相关的脑区。伏隔核(NAC)就是这样一个区域，它在奖赏和动机行为中发挥作用。应用免疫组织化学和逆行追踪技术，我们发现孤束核中的GLP-1神经元向NAC有一个较强的投射。我们假设NAC GLP-1RS的激活抑制了摄食。在给药后1、2和24小时，GLP-1以阈值以下剂量注入大鼠NAC核心区侧脑室，可显著减少摄食量。同样的剂量注射到NAC壳内不起作用。用脑室阈值下剂量的GLP-1R拮抗剂exendin(9-39)处理NAC核心，在治疗后2小时引起明显的吞噬反应，提示NAC核心GLP-1RS的内源性刺激在限制食物摄入量中起作用。有人认为GLP-1可以引起恶心，但我们发现NAC核心给予GLP-1不会引起对糖精的条件性味觉厌恶，这表明NAC核心GLP-1的厌食效应不是由恶心引起的。最后，我们观察到NAC核心注射GLP-1显著增加了NAC核心c-Fos的表达。我们认为NAC内的GLP-1受体在食物摄取控制中起着生理作用，提示GLP-1投射到NAC核心区可能将后脑的饱足信号处理与前脑的食物奖赏处理联系起来。
Central glucagon-like peptide 1 receptor (GLP-1R) stimulation suppresses food intake, and hindbrain GLP-1 neurons project to numerous feeding-relevant brain regions. One such region is the nucleus accumbens (NAc), which plays a role in reward and motivated behavior. Using immunohistochemical and retrograde tracing techniques in rats, we identified a robust projection from GLP-1 neurons in the nucleus of the solitary tract to the NAc. We hypothesized that activation of NAc GLP-1Rs suppresses feeding. When injected into the NAc core of rats at doses subthreshold for effect when administered to the lateral ventricle, GLP-1 significantly reduced food intake relative to vehicle at 1, 2, and 24 h posttreatment. The same doses had no effect when injected into the NAc shell. NAc core treatment with ventricle-subthreshold doses of the GLP-1R antagonist exendin (9–39) caused significant hyperphagia at 2 h posttreatment, suggesting that endogenous stimulation of NAc core GLP-1Rs plays a role in limiting food intake. It has been suggested that GLP-1 can cause nausea, but we found that NAc core administration of GLP-1 did not cause a conditioned taste aversion to saccharin, suggesting that the anorexic effect of NAc core GLP-1 is not caused by malaise. Finally, we observed that NAc core injection of GLP-1 significantly increased c-Fos expression in the NAc core. We conclude that that GLP-1Rs in the NAc play a physiologic role in food intake control, and suggest that the GLP-1 projection to NAc core may link satiation signal processing in the hindbrain with forebrain processing of food reward.