Spierling Samantha R, Kreisler Alison D, Williams Casey A, Fang Savannah Y, Pucci Sarah N, Kines Kelsey T, Zorrilla Eric P
Department of Neuroscience, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA, USA.
Department of Neuroscience, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA, USA.
Physiol Behav. 2018 Aug 1;192:3-16. doi: 10.1016/j.physbeh.2018.04.001. Epub 2018 Apr 11.
Compulsive binge eating is a hallmark of binge eating disorder and bulimia nervosa and is implicated in some obesity cases. Eating disorders are sexually dimorphic, with females more often affected than males. Animal models of binge-like eating based on intermittent access to palatable food exist; but, little is known regarding sex differences or individual vulnerability in these models with respect to the reinforcing efficacy of food, the development of compulsive- and binge-like eating, or associated changes in whole-body metabolism or body composition. Adolescent male (n = 24) and female (n = 32) Wistar rats were maintained on chow or a preferred, high-sucrose, chocolate-flavored diet in continuous or intermittent, extended access conditions. Body weight and composition, intake, fixed- and progressive-ratio operant self-administration, and whole body energy expenditure and respiratory exchange ratios were measured across an 11-week study period. Subgroup analyses were conducted to differentiate compulsive-like "high responder" intermittent access rats that escalated to extreme progressive-ratio self-administration performance vs. more resistant "low responders." Female rats had greater reinforcing efficacy of food than males in all diet conditions and were more often classified as "high responders". In both sexes, rats with intermittent access showed cycling of fuel substrate utilization and whole-body energy expenditure. Further, "high-responding" intermittent access female rats had especially elevated respiratory exchange ratios, indicating a fat-sparing phenotype. Future studies are needed to better understand the molecular and neurobiological basis of the sex and individual differences we have observed in rats and their translational impact for humans with compulsive, binge eating disorders.
强迫性暴饮暴食是暴饮暴食障碍和神经性贪食症的一个标志，在一些肥胖病例中也有涉及。饮食失调存在性别差异，女性比男性更容易受到影响。基于间歇性获取美味食物的暴饮暴食动物模型是存在的；但是，关于这些模型在食物强化效果、强迫性和暴饮暴食样行为的发展，或全身代谢或身体成分的相关变化方面的性别差异或个体易感性，我们所知甚少。将青春期雄性（n = 24）和雌性（n = 32）Wistar大鼠分别置于普通饲料或偏爱的高糖巧克力味饲料中，饲养条件为持续或间歇性、长时间获取。在为期11周的研究期间，测量大鼠的体重和身体成分、摄入量、固定比率和累进比率操作性自我给药情况，以及全身能量消耗和呼吸交换率。进行亚组分析，以区分强迫性“高反应者”间歇性获取组大鼠（这些大鼠在累进比率自我给药表现上升级到极端水平）和更具抵抗力的“低反应者”。在所有饮食条件下，雌性大鼠对食物的强化效果都比雄性大鼠更强，并且更常被归类为“高反应者”。在两性中，间歇性获取食物的大鼠都表现出燃料底物利用和全身能量消耗的循环变化。此外，“高反应性”间歇性获取食物的雌性大鼠的呼吸交换率尤其升高，表明具有脂肪节约型表型。未来需要开展更多研究，以更好地理解我们在大鼠中观察到的性别和个体差异的分子和神经生物学基础，以及它们对患有强迫性暴饮暴食障碍的人类的转化影响。
