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

肥胖和瘦 Zucker 大鼠的脂肪、甜味和可卡因强化

• 批准号: 8303664
• 负责人: Kevin B. Freeman
• 金额: $ 11.21万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8303664
• 关键词: Affect; American; Animals; Behavioral; Behavioral Assay; Behavioral Model; Biological Assay; Body Weight decreased; Brain; Canned Foods; Chronic; Cocaine; Corn Oil; Country; Development; Diagnostic; Diet; Disease; Drug Addiction; Drug abuse; Drug usage; Eating; Economics; Effectiveness of Interventions; Elements; Energy Metabolism; Epidemic; Exposure to; Fatty acid glycerol esters; Flavoring; Food; Food Energy; Genetic; Genetic Models; Hormones; Hyperphagia; Incidence; Individual; Ingestion; Intravenous; Investigation; Knowledge; Lead; Leptin; Macronutrients Nutrition; Methods; Modeling; Motivation; Mutation; Neurons; Non obese; Obesity; Outcome; Overweight; Pharmaceutical Preparations; Phenotype; Population; Psychological reinforcement; Public Health; Rat Strains; Rattus; Relative (related person); Research; Research Personnel; Rewards; Risk Factors; Saccharin; Satiation; Solutions; Specificity; Stimulus; System; Taste Perception; Testing; United States; Ursidae Family; Work; Zucker Rats; addiction; design; drug of abuse; drug reinforcement; effective intervention; food consumption; interest; neuroadaptation; novel; obesity treatment; pleasure; recidivism; reinforcer; research study; resistant strain; sugar; sweet taste perception; therapy design; trend

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.

描述（由申请人提供）：美国肥胖症的发病率正在上升。因此，人们对将肥胖视为一种与毒瘾具有共同特征的强迫症进行研究的兴趣有所增加。习惯性暴饮暴食会在大脑奖励系统中产生神经适应，类似于长期吸毒。然而，目前尚不清楚与肥胖相关的奖励系统的改变是否会对脂肪和糖这两种高度强化和能量密集的食物成分的相对价值产生不同的影响。此外，还不清楚肥胖引起的奖励变化如何影响滥用药物等非食物强化剂的价值。确定肥胖与饮食改变之间相互作用的范围非常重要，因为制定有效的干预措施需要了解维持暴饮暴食表型的特定脆弱性。研究这个问题的一种方法是使用肥胖遗传模型来测试脂肪、糖果和可卡因等非食物强化剂的相对强化作用。 Zucker 肥胖 (Ob) 大鼠广泛用于肥胖及相关疾病的研究。然而，它在食物奖励研究中的应用有限，并且尚未用滥用药物进行测试。因此，我提出三个具体目标。具体目标 1 将通过比较 Ob 大鼠和玉米油的奖励来检查脂肪的相对强化功效。 他们的瘦对应物是 Zucker 瘦 (Le) 老鼠。其次，我将通过比较特定目标 2 中 Ob 和 Le 大鼠的糖精奖励来研究甜味（糖强化的一个组成部分）的相对强化功效。最后，为了检查改变的奖励是否普遍适用于肥胖者的非食物强化，我将在具体目标 3 中比较 Ob 和 Le 大鼠静脉注射可卡因的强化功效。为了量化玉米油的相对增强功效， 糖精和可卡因，我将使用行为经济学，这是一种最先进的行为分析方法，非常适合根据价值缩放不同类型的强化物。我的假设是，肥胖状态与所有强化物价值的普遍增加有关。因此，我预计 Ob 大鼠比 Le 大鼠更看重玉米油、糖精和可卡因。该实验的结果将为建立测试肥胖与奖励之间相互作用的行为模型迈出第一步，并可能为测试旨在降低肥胖者食物奖励功效的干预措施提供新模型。 公共卫生相关性：肥胖是多种疾病的危险因素，其发病率在美国和许多其他国家已达到流行病水平。本申请中提出的实验将通过测试行为奖励系统（即快乐）中鼓励肥胖个体暴饮暴食的特定漏洞，提供与维持肥胖机制相关的基本信息。这些结果将通过提供有关肥胖者奖励脆弱性的信息来服务于公共健康利益，从而可能导致在肥胖治疗方面采取更有效的干预措施。

项目成果

Corn oil, but not cocaine, is a more effective reinforcer in obese than in lean Zucker rats.

玉米油（而非可卡因）对于肥胖的 Zucker 大鼠来说是比瘦的 Zucker 大鼠更有效的强化剂。

• 发表时间: 2015-05-01
• 影响因子: 2.9
• 作者: Townsend, Edward A;Beloate, Lauren N;Huskinson, Sally L;Roma, Peter G;Freeman, Kevin B
• 通讯作者: Freeman, Kevin B