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.
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.
|Huskinson, Sally L; Naylor, Jennifer E; Rowlett, James K et al. (2014) Predicting abuse potential of stimulants and other dopaminergic drugs: overview and recommendations. Neuropharmacology 87:66-80|