The inverse agonist of CB1 receptor SR141716 blocks compulsive eating of palatable food.
The inverse agonist of CB1 receptor SR141716 blocks compulsive eating of palatable food.
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DOI：
10.1111/adb.12056
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发表时间：
2014-09
影响因子：
3.4
通讯作者：
Cottone P
中科院分区：
文献类型：
--
作者：
Dore R;Valenza M;Wang X;Rice KC;Sabino V;Cottone P
节食和高可口食物的增加被认为是饮食失调和肥胖症大量发生的主要促成因素。本研究的目的是调查大麻素（CB）系统的作用，在一种新的动物模型的强迫进食，基于快速可口的饮食循环协议。雄性Wistar大鼠连续饲喂常规饲料（Chow/Chow，对照组）或间歇饲喂常规饲料2天和适口高蔗糖饲料1天（Chow/Palatable）。普通饲料/适口饲料大鼠在喂食常规饲料时表现出自发性和进行性增加的摄食量不足和体重减轻，在喂食适口饲料时表现出过量摄食和体重增加。饮食循环大鼠在重新进入的第一个小时内显著增加了可口饮食的摄入量（与对照组相比增加了7.5倍），并且在退出后，它们表现出强迫性进食和冒险行为。与对照组相比，CB 1受体反向激动剂SR 141716可降低Chow/Palatable大鼠中适口食物的过量摄入，效力更高，且对体重的疗效更大。此外，SR 141716可减少Chow/Palatable大鼠的强迫性进食和冒险行为。最后，与行为和药理学观察结果一致，与对照组相比，从适口饮食中撤出降低了下丘脑腹内侧脂肪酸酰胺水解酶的基因表达，同时增加了Chow/适口大鼠背侧纹状体中CB 1受体的基因表达。这些发现将有助于了解CB系统在强迫性进食中的作用。
Dieting and the increased availability of highly palatable food are considered major contributing factors to the large incidence of eating disorders and obesity. This study was aimed at investigating the role of the cannabinoid (CB) system in a novel animal model of compulsive eating, based on a rapid palatable diet cycling protocol. Male Wistar rats were fed either continuously a regular chow diet (Chow/Chow, control group) or intermittently a regular chow diet for 2 days and a palatable, high-sucrose diet for 1 day (Chow/Palatable). Chow/Palatable rats showed spontaneous and progressively increasing hypophagia and body weight loss when fed the regular chow diet, and excessive food intake and body weight gain when fed the palatable diet. Diet cycled rats dramatically escalated the intake of the palatable diet during the first hour of renewed access (7.5 fold compared to controls), and after withdrawal they showed compulsive eating and heightened risk-taking behavior. The inverse agonist of the CB1 receptor, SR141716 reduced the excessive intake of palatable food with higher potency and the body weight with greater efficacy in Chow/Palatable rats, compared to controls. Moreover, SR141716 reduced compulsive eating and risk-taking behavior in Chow/Palatable rats. Finally, consistent with the behavioral and pharmacological observations, withdrawal from the palatable diet decreased the gene expression of the enzyme fatty acid amide hydrolase in the ventromedial hypothalamus while increasing that of CB1 receptors in the dorsal striatum in Chow/Palatable rats, compared to controls. These findings will help understand the role of the CB system in compulsive eating.
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DOI：
10.1073/pnas.0707585104
发表时间：
2007-10-23
影响因子：
11.1
作者：
George, Olivier;Ghozland, Sandy;Koob, George F.
通讯作者：
Koob, George F.
影响因子：
4.2
作者：
Corwin, Rebecca L.;Grigson, Patricia S.
通讯作者：
Grigson, Patricia S.
影响因子：
82.9
作者：
De Vries, TJ;Shaham, Y;Schoffelmeer, ANM
通讯作者：
Schoffelmeer, ANM
影响因子：
5.4
作者：
Corwin, RL
通讯作者：
Corwin, RL
影响因子：
15.9
作者：
DiPatrizio NV;Piomelli D
通讯作者：
Piomelli D