Blasio Angelo, Rice Kenner C, Sabino Valentina, Cottone Pietro
aLaboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, Massachusetts bChemical Biology Research Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland, USA.
Behav Pharmacol. 2014 Oct;25(7):609-17. doi: 10.1097/FBP.0000000000000059.
The prevalence of eating disorders and obesity in western societies is epidemic and increasing in severity. Preclinical research has focused on the development of animal models that can mimic the maladaptive patterns of food intake observed in certain forms of eating disorders and obesity. This study was aimed at characterizing a recently established model of palatable diet alternation in female rats. For this purpose, females rats were fed either continuously with a regular chow diet (Chow/Chow) or intermittently with a regular chow diet for 2 days and a palatable, high-sucrose diet for 1 day (Chow/Palatable). Following diet cycling, rats were administered rimonabant (0, 0.3, 1, 3 mg/kg intraperitoneally) during access to either palatable diet or chow diet and were assessed for food intake and body weight. Finally, rats were pretreated with rimonabant (0, 3 mg/kg, intraperitoneally) and tested in the elevated plus maze during withdrawal from the palatable diet. Female rats with alternating access to palatable food cycled their intake, overeating during access to the palatable diet and undereating upon returning to the regular chow diet. Rimonabant treatment resulted in increased chow hypophagia and anxiety-like behavior in Chow/Palatable rats. No effect of drug treatment was observed on the compulsive eating of palatable food in the diet-cycled rats. The results of this study suggest that withdrawal from alternating access to the palatable diet makes individuals vulnerable to the anxiogenic effects of rimonabant and provides etiological factors potentially responsible for the emergence of severe psychiatric side-effects following rimonabant treatment in obese patients.
西方社会中饮食失调和肥胖的患病率呈流行趋势且严重程度不断增加。临床前研究聚焦于开发能够模拟在某些形式的饮食失调和肥胖中观察到的不良食物摄入模式的动物模型。本研究旨在描述一种最近建立的雌性大鼠美味饮食交替模型的特征。为此,将雌性大鼠连续喂食常规饲料(常规饲料/常规饲料),或间歇性地喂食常规饲料2天,再喂食美味的高糖饲料1天(常规饲料/美味饲料)。饮食循环后,在给予大鼠美味饮食或常规饲料时腹腔注射利莫那班(0、0.3、1、3毫克/千克),并评估其食物摄入量和体重。最后,对大鼠进行利莫那班预处理(0、3毫克/千克,腹腔注射),并在从美味饮食撤药期间在高架十字迷宫中进行测试。交替接触美味食物的雌性大鼠会循环其摄入量,在接触美味饮食时暴饮暴食,而回到常规饲料时则食量减少。利莫那班治疗导致常规饲料/美味饲料组大鼠的常规饲料摄食量减少和出现类似焦虑的行为。未观察到药物治疗对饮食循环大鼠对美味食物的强迫性进食有影响。本研究结果表明,从交替接触美味饮食中撤药会使个体易受利莫那班的致焦虑作用影响,并提供了肥胖患者接受利莫那班治疗后出现严重精神副作用的潜在病因。