Orexin/Hypocretin-1 Receptor Antagonism Selectively Reduces Cue-Induced Feeding in Sated Rats and Recruits Medial Prefrontal Cortex and Thalamus.
Orexin/Hypocretin-1 Receptor Antagonism Selectively Reduces Cue-Induced Feeding in Sated Rats and Recruits Medial Prefrontal Cortex and Thalamus.
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DOI：
10.1038/srep16143
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发表时间：
2015-11-05
影响因子：
4.6
通讯作者：
Petrovich GD
中科院分区：
文献类型：
--
作者：
Cole S;Mayer HS;Petrovich GD
食欲素/下丘脑泌素系统在奖赏寻求行为中起重要作用，但其在非稳态摄食中的作用却知之甚少。环境的影响，特别是食物的线索，可以刺激在没有饥饿的情况下进食，并导致适应不良的暴饮暴食行为。在饱足大鼠中，介导这种线索诱导的暴饮暴食的神经网络的关键组成部分包括外侧下丘脑、杏仁核和内侧前额叶皮质（mPFC），但该网络中的神经药理学机制仍然未知。目前的研究调查了食欲素的因果关系在线索驱动的进食，并检查了食欲素介导这种效果的神经基板。全身给予食欲素-1受体（OX 1 R）拮抗剂SB-334867对基线进食没有影响，但显著降低了饱足大鼠的线索驱动消耗。补充神经分析显示，SB-334867下减少线索诱导的摄食增加了mPFC和室旁丘脑中的Fos表达。这些结果表明，OX 1 R信号传导严格调节线索诱导的进食，并表明食欲素是通过前额叶皮层和丘脑网站驱动进食在没有饥饿。这些发现为我们了解食物相关的线索如何覆盖来自身体的信号以促进暴饮暴食提供了信息，并表明OX 1 R拮抗作用是治疗人类饮食失调的潜在药理学靶点。
The orexin/hypocretin system is important for reward-seeking behaviors, however less is known about its function in non-homeostatic feeding. Environmental influences, particularly cues for food can stimulate feeding in the absence of hunger and lead to maladaptive overeating behavior. The key components of the neural network that mediates this cue-induced overeating in sated rats include lateral hypothalamus, amygdala, and medial prefrontal cortex (mPFC), yet the neuropharmacological mechanisms within this network remain unknown. The current study investigated a causal role for orexin in cue-driven feeding, and examined the neural substrates through which orexin mediates this effect. Systemic administration of the orexin-1 receptor (OX1R) antagonist SB-334867 had no effect on baseline eating, but significantly reduced cue-driven consumption in sated rats. Complementary neural analysis revealed that decreased cue-induced feeding under SB-334867 increased Fos expression in mPFC and paraventricular thalamus. These results demonstrate that OX1R signaling critically regulates cue-induced feeding, and suggest orexin is acting through prefrontal cortical and thalamic sites to drive eating in the absence of hunger. These findings inform our understanding of how food-associated cues override signals from the body to promote overeating, and indicate OX1R antagonism as a potential pharmacologic target for treatment of disordered eating in humans.