Department of Physiology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Am J Physiol Regul Integr Comp Physiol. 2011 Jul;301(1):R244-54. doi: 10.1152/ajpregu.00406.2010. Epub 2011 May 4.
Infusion of a μ-opioid receptor (MOR) agonist into the nucleus accumbens (NAcc) drives voracious food intake, an effect hypothesized to occur through increased tastant palatability. While intake of many palatable foods is elevated by MOR stimulation, this manipulation has a preferential effect on fatty food ingestion. Consumption of high-fat foods is increased by NAcc MOR stimulation even in rats that prefer a carbohydrate-rich alternative under baseline conditions. This suggests that NAcc MOR stimulation may not simply potentiate palatability signals and raises the possibility that mechanisms mediating fat intake may be distinct from those underlying intake of other tastants. The present study was conducted to investigate the physiological mechanisms underlying the effects of NAcc MOR stimulation on fatty food intake. In experiment 1, we analyzed lick microstructure in rats ingesting Intralipid to identify the changes underlying feeding induced by infusion of a MOR-specific agonist into the NAcc. MOR stimulation in the NAcc core, but not shell, increased burst duration and first-minute licks, while simultaneously increasing the rate and duration of Intralipid ingestion. These results suggest that MOR activation in the core increases Intralipid palatability and attenuates inhibitory postingestive feedback. In experiment 2, we measured the effects of MOR stimulation in the NAcc core on consumption of nonnutritive olestra. A MOR-specific agonist dose dependently increased olestra intake, demonstrating that caloric signaling is not required for hyperphagia induced by NAcc MOR stimulation. Feeding induced by drug infusion in both experiments 1 and 2 was blocked by a MOR antagonist. In experiment 3, we determined whether MOR activation in the NAcc core could attenuate satiety-related signaling caused by infusion of the melanocortin agonist MTII into the third ventricle. Suppression of intake caused by MTII was reversed by MOR stimulation. Together, our results suggest that MOR stimulation in the NAcc core elevates fatty food intake through palatability mechanisms dependent on orosensory cues and suppression of satiety signals inhibiting food intake.
阿片μ型受体（MOR）激动剂输注至伏隔核（NAcc）会促使暴食，这一效应据推测是通过增加味觉可口性实现的。虽然许多可口食物的摄入都会因 MOR 刺激而增加，但这种操作对高脂肪食物的摄入有优先影响。即使在基线条件下更喜欢富含碳水化合物的替代物的大鼠中，NAcc MOR 刺激也会增加高脂肪食物的消耗。这表明 NAcc MOR 刺激可能不仅仅增强味觉可口性信号，并提出了调节脂肪摄入的机制可能与其他味觉物质摄入的机制不同的可能性。本研究旨在探讨 NAcc MOR 刺激对高脂肪食物摄入影响的生理机制。在实验 1 中，我们分析了摄入 Intralipid 的大鼠的舔舐微观结构，以确定 NAcc 内 MOR 特异性激动剂输注诱导进食的变化基础。NAcc 核心内而不是壳内的 MOR 刺激增加了爆发持续时间和前 1 分钟的舔舐次数，同时增加了 Intralipid 的摄入率和持续时间。这些结果表明，核心内的 MOR 激活增加了 Intralipid 的可口性，并减弱了抑制性摄食后反馈。在实验 2 中，我们测量了 NAcc 核心内 MOR 刺激对非营养性奥利斯特拉的消耗的影响。一种 MOR 特异性激动剂剂量依赖性地增加了奥利斯特拉的摄入量，证明 NAcc MOR 刺激引起的暴食不需要热量信号。在实验 1 和 2 中，药物输注诱导的进食均被 MOR 拮抗剂阻断。在实验 3 中，我们确定了 NAcc 核心内的 MOR 激活是否可以减弱第三脑室中黑色素皮质素激动剂 MTII 输注引起的饱腹感相关信号。MTII 引起的摄入量抑制被 MOR 刺激逆转。总之，我们的结果表明，NAcc 核心内的 MOR 刺激通过依赖于口味觉线索和抑制抑制食物摄入的饱腹感信号的可口性机制来提高高脂肪食物的摄入。
