Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA; Graduate Program for Neuroscience, Boston University School of Medicine, Boston, MA, USA.
Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.
Pharmacol Biochem Behav. 2017 Dec;163:1-8. doi: 10.1016/j.pbb.2017.10.013. Epub 2017 Oct 31.
Obesity and eating disorders are widespread in Western societies. Both the increased availability of highly palatable foods and dieting are major risk factors contributing to the epidemic of disorders of feeding. The purpose of this study was to characterize an animal model of maladaptive feeding induced by intermittent access to a palatable diet alternation in mice. In this study, mice were either continuously provided with standard chow food (Chow/Chow), or provided with standard chow for 2days and a high-sucrose, palatable food for 1day (Chow/Palatable). Following stability of intake within the cycling paradigm, we then investigated the effects of several pharmacological treatments on excessive eating of palatable food: naltrexone, an opioid receptor antagonist, SR141716A, a cannabinoid-1 receptor antagonist/inverse agonist, and BD-1063, a sigma-1 receptor antagonist. Over successive cycles, Chow/Palatable mice showed an escalation of palatable food intake within the first hour of renewed access to palatable diet and displayed hypophagia upon its removal. Naltrexone, SR141716A, and BD-1063 all reduced overconsumption of palatable food during this first hour. Here we provide evidence of strong face and convergent validity in a palatable diet alternation model in mice, confirming multiple shared underlying mechanisms of pathological eating across species, and thus making it a useful therapeutic development tool.
肥胖和饮食失调在西方社会普遍存在。高度美味的食物的可获得性增加和节食是导致进食障碍流行的主要危险因素。本研究的目的是描述一种通过间歇性接触美味饮食交替在小鼠中引起适应性进食障碍的动物模型。在这项研究中,小鼠要么连续提供标准的食物(Chow/Chow),要么提供标准食物 2 天,然后提供高蔗糖的美味食物 1 天(Chow/Palatable)。在循环范式内摄入量稳定后,我们研究了几种药物治疗对美味食物过度摄入的影响:纳曲酮,一种阿片受体拮抗剂;SR141716A,一种大麻素-1 受体拮抗剂/反向激动剂;BD-1063,一种 sigma-1 受体拮抗剂。在连续的循环中,Chow/Palatable 组小鼠在重新接触美味饮食的第一个小时内显示出美味食物摄入量的增加,并在其被移除时表现出摄食量减少。纳曲酮、SR141716A 和 BD-1063 都减少了在这第一个小时内对美味食物的过度摄入。在这里,我们在小鼠的美味饮食交替模型中提供了强烈的表面和收敛有效性的证据,证实了跨物种病理性进食的多个共同潜在机制,因此使其成为一种有用的治疗开发工具。