Fat, sweet taste, and cocaine reinforcement in obese and lean Zucker rats

描述（由申请人提供）：美国的肥胖发病率正在上升。因此，将肥胖作为一种与药物成瘾有共同特征的强迫性障碍进行研究的兴趣有所增加。习惯性暴饮暴食在大脑奖励系统中产生神经适应性，类似于慢性吸毒。然而，目前尚不清楚与肥胖相关的奖励系统改变是否会不同地影响脂肪和糖的相对价值，这两种食物的高强化和高能量成分。此外，肥胖带来的奖励变化如何影响非食物强化物（如滥用药物）的价值也尚不清楚。确定肥胖和改变的强化评价之间相互作用的范围很重要，因为开发有效的干预措施将需要了解维持暴饮暴食表型的特定脆弱性。研究这一问题的一种方法是使用肥胖的遗传模型来测试脂肪、糖果和非食物（如可卡因）的相对强化效应。Zucker肥胖（Ob）大鼠被广泛用于肥胖及相关疾病的研究。然而，它在食物奖励的研究中得到了有限的应用，并且尚未与滥用药物进行测试。因此，我提出三个具体目标。具体目的1将通过比较玉米油在大鼠和大鼠中的奖励来检验脂肪的相对强化作用

DESCRIPTION (provided by applicant): The incidence of obesity is rising in the United States. Accordingly, interest in examining obesity as a compulsive disorder sharing features with drug addiction has increased. Habitual overeating produces neuroadaptations in brain reward systems similar to chronic drug use. However, it is currently unclear if altered reward systems associated with obesity differentially affect the relative values of fat and sugar, two highly-reinforcing and energy-dense constituents of food. Furthermore, it is also unclear how reward alterations with obesity affect the value of non-food reinforcers like drugs of abuse. Identifying the scope of interaction between obesity and altered reinforces valuation is important because the development of effective interventions will require knowledge of the specific vulnerabilities that maintain an overeating phenotype. One approach to the investigation of this issue is to use a genetic model of obesity to test the relative reinforcing effects of fats, sweets, and non-food reinforces such as cocaine. The Zucker obese (Ob) rat is widely used in the study of obesity and related disorders. However, it has received limited use in the study of food reward and has yet to be tested with a drug of abuse. I am therefore proposing three specific aims. Specific Aim 1 will examine the relative reinforcing efficacy of fat by comparing corn oil reward in Ob rats and their lean counterparts, the Zucker lean (Le) rat. Secondly, I will investigate the relative reinforcing efficacy of sweet taste, a component of sugar reinforcement, by comparing saccharin reward in Ob and Le rats in Specific Aim 2. Finally, to examine if altered reward generalizes to non-food reinforces in the obese, I will in Specific Aim 3 compare the reinforcing efficacy of intravenous cocaine in Ob and Le rats. To quantify the relative reinforcing efficacies of corn oil, saccharin, and cocaine, I will use behavioral economics, a state-of-the-art behavioral assay that is well-suited for the scaling of reinforcers of different types according to value. It is my hypothesis that the obese state is associated with a general increase in the value of all reinforcers. As such, I expect the Ob rat to value corn oil, saccharin, and cocaine to a greater degree than Le rats. The results of this experiment will provide a first step towards establishing a behavioral model for testing interactions between obesity and reward and may provide a novel model for testing interventions designed to reduce the efficacy of food reward in the obese. PUBLIC HEALTH RELEVANCE: Obesity is a risk factor for a number of diseases, and its incidence has reached epidemic levels in the United States and in many other countries. The experiments proposed in this application will provide basic information relevant to mechanisms that maintain obesity by testing for specific vulnerabilities in the behavioral reward system (i.e. pleasure) that encourage obese individuals to overeat. These results will serve public health interests by providing information about reward vulnerabilities in the obese, which may then lead to more effective interventions in the treatment of obesity.