Cook Jason B, Hendrickson Linzy M, Garwood Grant M, Toungate Kelsey M, Nania Christina V, Morikawa Hitoshi
Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, United States of America.
Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, United States of America.
PLoS One. 2017 Aug 31;12(8):e0183685. doi: 10.1371/journal.pone.0183685. eCollection 2017.
Similar to drugs of abuse, the hedonic value of food is mediated, at least in part, by the mesostriatal dopamine (DA) system. Prolonged intake of either high calorie diets or drugs of abuse both lead to a blunting of the DA system. Most studies have focused on DAergic alterations in the striatum, but little is known about the effects of high calorie diets on ventral tegmental area (VTA) DA neurons. Since high calorie diets produce addictive-like DAergic adaptations, it is possible these diets may increase addiction susceptibility. However, high calorie diets consistently reduce psychostimulant intake and conditioned place preference in rodents. In contrast, high calorie diets can increase or decrease ethanol drinking, but it is not known how a junk food diet (cafeteria diet) affects ethanol drinking. In the current study, we administered a cafeteria diet consisting of bacon, potato chips, cheesecake, cookies, breakfast cereals, marshmallows, and chocolate candies to male Wistar rats for 3-4 weeks, producing an obese phenotype. Prior cafeteria diet feeding reduced homecage ethanol drinking over 2 weeks of testing, and transiently reduced sucrose and chow intake. Importantly, cafeteria diet had no effect on ethanol metabolism rate or blood ethanol concentrations following 2g/kg ethanol administration. In midbrain slices, we showed that cafeteria diet feeding enhances DA D2 receptor (D2R) autoinhibition in VTA DA neurons. These results show that junk food diet-induced obesity reduces ethanol drinking, and suggest that increased D2R autoinhibition in the VTA may contribute to deficits in DAergic signaling and reward hypofunction observed with obesity.
与滥用药物类似，食物的享乐价值至少部分由中脑纹状体多巴胺（DA）系统介导。长期摄入高热量饮食或滥用药物都会导致DA系统反应迟钝。大多数研究都集中在纹状体中多巴胺能的改变上，但对于高热量饮食对腹侧被盖区（VTA）多巴胺能神经元的影响却知之甚少。由于高热量饮食会产生类似成瘾的多巴胺能适应性变化，因此这些饮食有可能增加成瘾易感性。然而，高热量饮食持续减少啮齿动物的精神兴奋剂摄入量和条件性位置偏好。相比之下，高热量饮食可以增加或减少乙醇摄入量，但垃圾食品饮食（自助餐饮食）如何影响乙醇摄入量尚不清楚。在本研究中，我们给雄性Wistar大鼠喂食由培根、薯片、芝士蛋糕、饼干、早餐谷物、棉花糖和巧克力糖果组成的自助餐饮食3 - 4周，使其呈现肥胖表型。在2周的测试期内，先前的自助餐饮食喂养减少了笼内乙醇摄入量，并短暂降低了蔗糖和食物摄入量。重要的是，在给予2g/kg乙醇后，自助餐饮食对乙醇代谢率或血液乙醇浓度没有影响。在中脑切片中，我们发现自助餐饮食喂养增强了VTA多巴胺能神经元中的DA D2受体（D2R）自身抑制作用。这些结果表明，垃圾食品饮食诱导的肥胖会减少乙醇摄入量，并表明VTA中D2R自身抑制作用增强可能导致肥胖时观察到的多巴胺能信号传导缺陷和奖赏功能减退。
