Translational Neuroscience Program, Department of Psychiatry, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA.
Neuropsychopharmacology. 2013 Aug;38(9):1685-97. doi: 10.1038/npp.2013.66. Epub 2013 Mar 8.
The ability of amylin, a pancreatic β-cell-derived neuropeptide, to promote negative energy balance has been ascribed to neural activation at the area postrema. However, despite amylin binding throughout the brain, the possible role of amylin signaling at other nuclei in the control of food intake has been largely neglected. We show that mRNA for all components of the amylin receptor complex is expressed in the ventral tegmental area (VTA), a mesolimbic structure mediating food intake and reward. Direct activation of VTA amylin receptors reduces the intake of chow and palatable sucrose solution in rats. This effect is mediated by reductions in meal size and is not due to nausea/malaise or prolonged suppression of locomotor activity. VTA amylin receptor activation also reduces sucrose self-administration on a progressive ratio schedule. Finally, antagonist studies provide novel evidence that VTA amylin receptor blockade increases food intake and attenuates the intake-suppressive effects of a peripherally administered amylin analog, suggesting that amylin receptor signaling in the VTA is physiologically relevant for food intake control and potentially clinically relevant for the treatment of obesity.
胰岛淀粉样多肽是一种由胰岛β细胞分泌的神经肽，它具有促进能量负平衡的能力，这归因于后极区的神经激活。然而，尽管胰岛淀粉样多肽在整个大脑中结合，但胰岛淀粉样多肽信号在其他核团中对摄食控制的可能作用在很大程度上被忽视了。我们发现，所有胰岛淀粉样多肽受体复合物成分的 mRNA 都在腹侧被盖区（VTA）中表达，VTA 是介导摄食和奖励的中脑边缘结构。直接激活 VTA 中的胰岛淀粉样多肽受体可减少大鼠的食物摄入量和美味蔗糖溶液的摄入量。这种作用是通过减少餐量来介导的，而不是由于恶心/不适或运动活动的长时间抑制。VTA 中的胰岛淀粉样多肽受体激活也减少了蔗糖的自我给药，即在递增比率方案上。最后，拮抗剂研究提供了新的证据，表明 VTA 中的胰岛淀粉样多肽受体阻断可增加食物摄入量，并减弱外周给予的胰岛淀粉样多肽类似物的摄食抑制作用，这表明 VTA 中的胰岛淀粉样多肽受体信号对食物摄入控制具有生理相关性，并且可能对肥胖症的治疗具有临床相关性。
