Leptin Signaling in the Medial Nucleus Tractus Solitarius Reduces Food Seeking and Willingness to Work for Food
Leptin Signaling in the Medial Nucleus Tractus Solitarius Reduces Food Seeking and Willingness to Work for Food
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DOI：
10.1038/npp.2013.235
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发表时间：
2014-02-01
影响因子：
7.6
通讯作者：
Grill, Harvey J.
中科院分区：
文献类型：
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作者：
Kanoski, Scott E.;Alhadeff, Amber L.;Grill, Harvey J.
脂肪源性激素瘦素在内侧孤束核（mNTS）中发出信号，部分通过放大餐内胃肠道（GI）饱足信号来抑制食物摄入。在这里，我们表明，mNTS瘦素受体（LepRb）信号也降低了食欲和动机方面的喂养，这些影响可以取决于能量状态。使用最低剂量，显着抑制3小时累积食物摄入量，单方面瘦素（0.3微克）管理的mNTS（3小时前测试）减少操作性杠杆按蔗糖下增加工作要求（渐进比例强化计划），无论动物是否是能量耗尽（食物限制）或充满（随意喂养）。然而，在一个单独的测试中的食物动机的反应，其中有没有机会消耗食物（条件性位置偏好（CPP）的环境以前与可口的食物奖励），mNTS瘦素管理抑制觅食行为，只有在长期食物限制的大鼠。另一方面，无论能量状态如何，mNTS LepRb信号传导都不会降低吗啡强化的CPP表达，这表明mNTS瘦素信号传导差异地影响食物与阿片奖励的动机性反应。总体结果表明，mNTS LepRb信号减少食物的摄入量和食欲的食物动机的反应独立的能量状态的情况下，涉及orosensory和postingestive接触食物，而寻求食物的行为独立的食物消耗只减少了mNTS LepRb激活的能量不足的状态。这些发现揭示了LepRb信号在mNTS中的一种新的食欲作用，mNTS是一个传统上与膳食相关的GI饱足信号处理相关的大脑区域。
The adipose-derived hormone leptin signals in the medial nucleus tractus solitarius (mNTS) to suppress food intake, in part, by amplifying within-meal gastrointestinal (GI) satiation signals. Here we show that mNTS leptin receptor (LepRb) signaling also reduces appetitive and motivational aspects of feeding, and that these effects can depend on energy status. Using the lowest dose that significantly suppressed 3-h cumulative food intake, unilateral leptin (0.3 mu g) administration to the mNTS (3 h before testing) reduced operant lever pressing for sucrose under increasing work demands (progressive ratio reinforcement schedule) regardless of whether animals were energy deplete (food restricted) or replete (ad libitum fed). However, in a separate test of food-motivated responding in which there was no opportunity to consume food (conditioned place preference (CPP) for an environment previously associated with a palatable food reward), mNTS leptin administration suppressed food-seeking behavior only in chronically food-restricted rats. On the other hand, mNTS LepRb signaling did not reduce CPP expression for morphine reinforcement regardless of energy status, suggesting that mNTS leptin signaling differentially influences motivated responding for food vs opioid reward. Overall results show that mNTS LepRb signaling reduces food intake and appetitive food-motivated responding independent of energy status in situations involving orosensory and postingestive contact with food, whereas food-seeking behavior independent of food consumption is only reduced by mNTS LepRb activation in a state of energy deficit. These findings reveal a novel appetitive role for LepRb signaling in the mNTS, a brain region traditionally linked with processing of meal-related GI satiation signals.