Amylin Receptor Signaling in the Nucleus Accumbens Negatively Modulates μ-opioid-Driven Feeding
Amylin Receptor Signaling in the Nucleus Accumbens Negatively Modulates μ-opioid-Driven Feeding
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DOI：
10.1038/npp.2014.153
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发表时间：
2014-12-01
影响因子：
7.6
通讯作者：
Baldo, Brian A.
中科院分区：
文献类型：
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作者：
Baisley, Sarah K.;Baldo, Brian A.
胰淀素是一种与胰岛素共同分泌的多肽，可以渗透到大脑中，并通过脑干、下丘脑和中脑的作用产生饱腹感。然而，人们对伏隔核壳中胰淀素的影响知之甚少，在那里，一个强烈的胰淀素受体(AMY-R)结合的限定区域与已报道的食物奖励的u-阿片受体(Mu-OR)放大的“热点”图谱重叠。在这里，我们探索了AcbSh AMY-R内信号调节FT-OR驱动的摄食的能力。将胰淀素(1-30 ng)与D-Ala2，N-MePhe4，Gly-ol]-脑啡肽(DAMGO)(0.25ug)一起直接注入自由活动大鼠的AcbSh。胰淀素呈剂量依赖性地逆转DAMGO诱导的吞噬作用；3 ng的胰淀素可使DAMGO介导的摄食减少近50%。然而，该剂量在改变DAMGO诱导的前背侧纹状体的摄食方面完全无效。单独注射AcbSh胰淀素(3-30 ng)可适度抑制自由活动维持的大鼠10%的蔗糖摄入量，并抑制食物匮乏大鼠的进食，但仅限于30 ng剂量。这一结果表明，剂量降低10倍的AcbSh DAMGO诱导的摄食逆转既不是由于不适也不是由于运动障碍。最后，AcbSh内注入AMY-R拮抗剂AC187(20微克)，显著减弱了预喂养抑制DAMGO诱导的摄食的能力，而对未预喂养的大鼠没有影响。因此，AMY-R信号在AcbSh的水平上负向地调节Mu-OR介导的食欲反应。AC187的结果表明，AcbSh的内源性AMY-R传递抑制了餐后阿片类药物的功能，这表明外周-中枢整合在控制食欲动机和阿片奖励方面是一条新的途径。
Amylin is a peptide co-secreted with insulin that penetrates into the brain, and produces satiation-like effects via actions in the brainstem, hypothalamus, and mesencephalon. Little is known, however, about the effects of amylin in the nucleus accumbens shell (AcbSh), where a circumscribed zone of intense amylin receptor (AMY-R) binding overlaps reported mappings of a 'hotspot' for mu-opioid receptor (mu-OR) amplification of food reward. Here, the ability of intra-AcbSh AMY-R signaling to modulate ft-OR-driven feeding was explored. Amylin (1-30 ng) was administered with the, mu-OR agonist, D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) (0.25 mu g), directly into the AcbSh of ad libitum-maintained rats. Amylin dose-dependently reversed DAMGO-induced hyperphagia; 3 ng of amylin reduced DAMGO-mediated feeding by nearly 50%. This dose was, however, completely ineffective at altering DAMGO-induced feeding in the anterior dorsal striatum. Intra-AcbSh amylin alone (3-30 ng) modestly suppressed 10% sucrose intake in ad libitum-maintained rats, and chow in food-deprived rats, but only at the 30-ng dose. This result indicates that reversal of AcbSh DAMGO-induced feeding at a 10-fold lower dose was neither due to malaise nor motoric impairment. Finally, intra-AcbSh infusion of the AMY-R antagonist, AC187 (20 mu g), significantly attenuated the ability of prefeeding to suppress DAMGO-induced food intake, with no effects in non-prefed rats. Hence, AMY-R signaling negatively modulates mu-OR-mediated appetitive responses at the level of the AcbSh. The results with AC187 indicate that endogenous AMY-R transmission in the AcbSh curtails opioid function in the postprandial period, suggesting a novel pathway for peripheral-central integration in the control of appetitive motivation and opioid reward.