Vollbrecht Peter J, Nobile Cameron W, Chadderdon Aaron M, Jutkiewicz Emily M, Ferrario Carrie R
Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
Physiol Behav. 2015 Dec 1;152(Pt A):151-60. doi: 10.1016/j.physbeh.2015.09.022. Epub 2015 Sep 28.
Obesity is a significant problem in the United States, with roughly one third of adults having a body mass index (BMI) over thirty. Recent evidence from human studies suggests that pre-existing differences in the function of mesolimbic circuits that mediate motivational processes may promote obesity and hamper weight loss. However, few preclinical studies have examined pre-existing neurobehavioral differences related to the function of mesolimbic systems in models of individual susceptibility to obesity. Here, we used selectively bred obesity-prone and obesity-resistant rats to examine 1) the effect of a novel "junk-food" diet on the development of obesity and metabolic dysfunction, 2) over-consumption of "junk-food" in a free access procedure, 3) motivation for food using instrumental procedures, and 4) cocaine-induced locomotor activity as an index of general mesolimbic function. As expected, eating a sugary, fatty, "junk-food" diet exacerbated weight gain and increased fasted insulin levels only in obesity-prone rats. In addition, obesity-prone rats continued to over-consume junk-food during discrete access testing, even when this same food was freely available in the home cage. Furthermore, when asked to press a lever to obtain food in an instrumental task, rates of responding were enhanced in obesity-prone versus obesity-resistant rats. Finally, obesity-prone rats showed a stronger locomotor response to 15 mg/kg cocaine compared to obesity-resistant rats prior to any diet manipulation. This enhanced sensitivity to this dose of cocaine is indicative of basal differences in the function of mesolimbic circuits in obesity-prone rats. We speculate that pre-existing differences in motivational systems may contribute to over-consumption and enhanced motivation in susceptible individuals.
肥胖在美国是一个严重问题，约三分之一的成年人身体质量指数（BMI）超过30。近期人体研究证据表明，介导动机过程的中脑边缘回路功能的既有差异可能会促进肥胖并阻碍体重减轻。然而，很少有临床前研究在个体易患肥胖症模型中检验与中脑边缘系统功能相关的既有神经行为差异。在此，我们使用选择性培育的肥胖倾向型和肥胖抵抗型大鼠来研究：1）新型“垃圾食品”饮食对肥胖和代谢功能障碍发展的影响；2）在自由获取程序中“垃圾食品”的过量摄入；3）使用操作性程序对食物的动机；4）可卡因诱导的运动活动作为一般中脑边缘功能的指标。正如预期的那样，食用含糖、高脂肪的“垃圾食品”仅在肥胖倾向型大鼠中加剧了体重增加并提高了空腹胰岛素水平。此外，在离散获取测试期间，肥胖倾向型大鼠继续过量食用垃圾食品，即使这种相同的食物在笼舍中可自由获取。此外，在一项操作性任务中，当要求大鼠按压杠杆以获取食物时，肥胖倾向型大鼠的反应率高于肥胖抵抗型大鼠。最后，在任何饮食干预之前，与肥胖抵抗型大鼠相比，肥胖倾向型大鼠对15mg/kg可卡因表现出更强的运动反应。对该剂量可卡因的这种增强敏感性表明肥胖倾向型大鼠中脑边缘回路功能存在基础差异。我们推测，动机系统的既有差异可能导致易感个体的过量摄入和动机增强。
