The Role of Ghrelin in Reward-Based Feeding

Abstract

The incidence of obesity has nearly doubled in the last 30 years, and this rise in incidence is directly linked to increased consumption of energy-dense foods. In addition, the majority of people attempting to lose weight report relapse to high fat foods while dieting. Recent studies suggest that the orexigenic hormone ghrelin can bind to dopaminergic cells in the ventral tegmental area (VTA), a key structure in the brain's reward system, and increase the incentive value of such foods. Specifically, studies have shown that ghrelin increases the motivation to work for food rewards, enhances the preference for contexts associated with food rewards, and augments the locomotor and physiological responses associated with food rewards. The experiments described in the present thesis aimed to establish the role of ghrelin in 2 additional reward-based feeding behaviours thought to contribute to the current obesity epidemic. The first behaviour is the consumption of palatable desserts after meals that adequately satisfy an individual's energetic demands. The second behaviour is the tendency to relapse to food seeking after a period of abstinence. In order to accomplish this, we compared ghrelin receptor knock out (KO) rats to rats possessing an identical genetic background, with an intact ghrelin receptor gene (wildtype rats -WT) in tasks designed to model these behaviours. In addition, we examined outbred rats receiving chronic infusions of either ghrelin or a ghrelin receptor antagonist in the VTA. Overall, the data presented in this thesis confirmed the role of ghrelin signalling in dessert consumption; KO rats ate less cookie dough when sated than WT rats. KO and WT rats performed similarly in operant conditioning and conditioned place preference models of relapse, also known as the operant and CPP reinstatement tests. In contrast, pharmacological action at the ghrelin ! iii! receptor in outbred rats could enhance and attenuate the expression of reinstatement of food seeking that is induced by food reward cues following administration of ghrelin and a ghrelin receptor antagonist, respectively. It is therefore likely that ghrelin is involved in the tendency to relapse to unhealthy eating habits in dieting individuals, and that this effect is due, in part, to its action in the reward system, particularly within the VTA. ! iv!