Evaluating Time-Dependent Changes in Food Seeking Following Periods of Forced Abstinence and Associated Changes in the Nucleus Accumbens

Abstract

Incubation of craving is a phenomenon whereby responding for cues associated with reward (food and drugs) increases over extended periods of abstinence. Evaluating the mechanisms of food craving has implications in understanding how consumption of foods high in certain macronutrients (fat, sugar) may contribute to continued cravings and subsequent weight gain. The primary goals of this thesis were to examine if forced abstinence from different food rewards resulted in a continued/or delayed craving response by utilizing different behavioral designs (contingent vs non-contingent) and examining associated changes in nucleus accumbens (NAc) immediate early genes, dendritic spine density, and AMPA receptor protein expression. Food self-administration (operant conditioning), classical conditioning, and conditioned place preference (CPP) were utilize for the investigation of incubation of food craving. Abstinence from selfadministration of purified food pellets was the only food group to display an incubation of craving response. Self-administration of chocolate flavored pellet, sucrose, or chocolate sucrose pellets did not result in an incubation response but did result in consistent responding at all abstinence periods which was associated with elevated dendritic spine density for chocolate flavored pellets. The type of behavioral design affected association FosB labelling as rats that underwent classical conditioning displayed significantly lower FosB in the NAc compared to operant trained rats and food restricted controls. CPP for chocolate flavored pellets or milk chocolate chips showed that the type of food reward can affect the possibility of a place preference response, milk chocolate did not produce CPP. The CPP model was unable to produce an incubation of craving response which may have resulted from the rewarding properties of the food choice and number of training sessions. Exposure to rewarding cues rapidly increased GluR1 expression, but this was not specifically associated with an incubation of craving response, thus the functional significance has yet to be elucidated. The present thesis has highlighted that foods of different macronutrient composition and/or flavors and the use of different behavioral designs can affect the potential for an incubation of craving response and associated NAc changes.