The Effects of Prolonged High Fat Diet Consumption on Feeding Behavior and Dopamine Signaling

Obesity is a costly epidemic that claims an escalating number of lives with each passing year. Despite its complex etiology, one key tenet that is widely accepted in the development of obesity is the overconsumption of calorically-enriched foods. These foods are easily accessible, and their consumption is promoted by the brain’s reward circuitry which consists primarily of the dopaminergic projections from the ventral tegmental area of the midbrain to the nucleus accumbens of the basal forebrain. This neural circuit, often referred to as the mesolimbic dopamine signaling pathway, is a key player in regulating various aspects of feeding behavior. However, the precise manner in which this circuitry and its attendant feeding behaviors respond to the prolonged consumption of energy-dense diets has yet to be fully elucidated. The work contained in this dissertation demonstrates that prolonged consumption of a high fat diet leads to food reward devaluation and alterations in preference that are reversible by dieting or exercise. In addition, we found that intact dopamine-1 receptor mediated signaling is essential for maintenance of food preference, and that high fat diet consumption desensitizes the response of the ventral tegmental area to palatable food reward. Our findings highlight a novel role for high fat diet consumption in the perturbation of both feeding behavior and relevant neural circuitry.