The role of ghrelin in Pavlovian and instrumental learning and performance

Abstract

Ghrelin is an orexigenic peptide that binds to the growth hormone secretagogue receptor (GHS-R). While it is known for regulating homeostatic feeding, recent research has revealed a role for ghrelin in reward-seeking. Missing from this research, however, is a systematic investigation into the role of ghrelin in reward-seeking: it is unclear whether ghrelin provides a reward signal, energises instrumental actions that earn palatable foods, or affects the ability of Pavlovian food-paired cues or food itself to invigorate instrumental responding, either generally or through the retrieval of specific associations. Given these phenomena promote overeating and weight gain, this thesis examined the role of ghrelin in Pavlovian and instrumental learning and performance. Overall, it was found that while ghrelin does not participate in Pavlovian or instrumental learning, it does modulate effort/response vigour: GHS-R antagonism attenuated established instrumental and progressive ratio responding for palatable food in rats. GHS-R antagonism had no effect on outcome devaluation, confirming that ghrelin affects instrumental responding by modulating effort/response vigour and not a change in outcome value. GHS-R antagonism had no effect on the return of responding driven by re-exposure to food after extinction (outcome-induced and outcome-specific reinstatement), and attenuated the general but not specific form of Pavlovian-instrumental transfer (PIT). Thus, ghrelin is also involved in the ability of Pavlovian food-paired cues to enhance instrumental responding based on a general excitatory relationship with food reward. As ghrelin levels fluctuate with changes in hunger/satiety, this thesis also investigated whether changes in ghrelin signalling recapitulate the effects of hunger/satiety. Generally, satiety had similar effects but was a more consistent modulator of instrumental performance and general PIT.