Investigating the Role of the Growth Hormone Secretagogue Receptor in Food-Motivated Behaviours

Ghrelin is a peptide produced in the gut that stimulates food intake.Action of ghrelin on its receptor, the GHSR, contributes to food motivated behaviours.Studies have found that the GHSR facilitates the activity of mesolimbic DA circuitry, promoting intake of highly palatable sugar or fat rich foods.Understanding what makes such foods attractive and rewarding may allow for behavioural, genetic, or pharmacological therapeutics to mitigate problematic overconsumption.The primary goals of this dissertation were to determine the consequences of interrupted GHSR signaling on food motivated behaviours, including binge-like feeding, and to examine whether GHSR in the VTA are an important neural substrate for the development and maintenance of such behavior.Operant responding for sucrose on a PR schedule of reinforcement, a measure of motivation to obtain a food reward, was diminished when rats lacked functional GHSR.These rats also spent less time in an environment previously paired with sucrose, suggesting a possible reward deficit as a result of loss of GHSR.GHSR null mice also consumed less sucrose in a two-bottle choice test in their home cage, and rescue of GHSR in the VTA was able to restore their preference for sucrose to the level of WT mice, implicating the VTA as a key node for GHSRs influence on preference for sweets.In a limited access model of high-fat binge eating, we found that GHSR KO mice binged less on fat than WT mice.Though, in our subsequent study, we found less robust effects of genotype on binge eating behavior, and rescue of GHSR in the VTA did not influence binge eating of fat.Further, pharmacological antagonism of the GHSR was not sufficient to reduce binge eating of high-fat in mice once established, indicating that the VTA is not the primary site of GHSRs influence on fat bingeing.Further studies examining ghrelin and the GSHR as moderators of food reward behavior are warranted, as it is likely that signaling through the GHSR promotes the associative learning induced by palatable food cues, as well as the motivation to obtain such foods, which may facilitate overconsumption.iiiAcknowledgements.I would like to thank my supervisor, Dr. Alfonso Abizaid, for the guidance, encouragement and advice he has provided me during my time in his lab.I consider myself lucky to have worked under his supervision and appreciate the freedom he offered me to pursue my research interests.His patience and compassion also helped me continue at times I thought I could

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