Mendez Ian A, Ostlund Sean B, Maidment Nigel T, Murphy Niall P
Hatos Center, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
1] Hatos Center, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA [2] Department of Anesthesiology and Perioperative Care, University of California, Irvine, Irvine, CA, USA.
Neuropsychopharmacology. 2015 Aug;40(9):2103-12. doi: 10.1038/npp.2015.67. Epub 2015 Mar 10.
Studies implicate opioid transmission in hedonic and metabolic control of feeding, although roles for specific endogenous opioid peptides have barely been addressed. Here, we studied palatable liquid consumption in proenkephalin knockout (PENK KO) and β-endorphin-deficient (BEND KO) mice, and how the body weight of these mice changed during consumption of an energy-dense highly palatable 'cafeteria diet'. When given access to sucrose solution, PENK KOs exhibited fewer bouts of licking than wild types, even though the length of bouts was similar to that of wild types, a pattern that suggests diminished food motivation. Conversely, BEND KOs did not differ from wild types in the number of licking bouts, even though these bouts were shorter in length, suggesting that they experienced the sucrose as being less palatable. In addition, licking responses in BEND, but not PENK, KO mice were insensitive to shifts in sucrose concentration or hunger. PENK, but not BEND, KOs exhibited lower baseline body weights compared with wild types on chow diet and attenuated weight gain when fed cafeteria diet. Based on this and related findings, we suggest endogenous enkephalins primarily set a background motivational tone regulating feeding behavior, whereas β-endorphin underlies orosensory reward in high need states or when the stimulus is especially valuable. Overall, these studies emphasize complex interplays between endogenous opioid peptides targeting μ-receptors, such as enkephalins and endorphins, underlying the regulation of feeding and body weight that might explain the poor efficacy of drugs that generally target μ-opioid receptors in the long-term control of appetite and body weight.
研究表明阿片类物质传递参与进食的享乐和代谢控制，尽管特定内源性阿片肽的作用几乎未被探讨。在此，我们研究了前脑啡肽基因敲除（PENK KO）小鼠和β-内啡肽缺陷（BEND KO）小鼠对美味液体的摄取情况，以及这些小鼠在食用能量密集型高美味“自助餐饮食”期间体重如何变化。当给予蔗糖溶液时，PENK KO小鼠的舔舐次数比野生型小鼠少，尽管每次舔舐的时长与野生型小鼠相似，这种模式表明其食物动机减弱。相反，BEND KO小鼠的舔舐次数与野生型小鼠没有差异，尽管每次舔舐的时长较短，这表明它们觉得蔗糖的美味程度较低。此外，BEND KO小鼠而非PENK KO小鼠的舔舐反应对蔗糖浓度变化或饥饿不敏感。与食用普通饲料的野生型小鼠相比，PENK KO小鼠而非BEND KO小鼠的基线体重较低，且在喂食自助餐饮食时体重增加减缓。基于此及相关发现，我们认为内源性脑啡肽主要设定调节进食行为的背景动机基调，而β-内啡肽在高需求状态下或刺激特别有价值时构成口感觉奖赏的基础。总体而言，这些研究强调了靶向μ受体的内源性阿片肽（如脑啡肽和内啡肽）之间复杂的相互作用，这些相互作用是进食和体重调节的基础，这可能解释了一般靶向μ阿片受体的药物在长期控制食欲和体重方面疗效不佳的原因。
