Stranger Danger! The Role of Ghrelin in Modulation of Social Behavior

Abstract

Ghrelin is a gut-derived peptide hormone associated with feeding, energy balance, reward and the stress response. Among many of its identified functions, the role of ghrelin in anxiety has been particularly controversial with some authors reporting anxiogenic and others reporting anxiolytic effects of ghrelin receptor activity. In this thesis, we demonstrated that increasing ghrelin receptor activity in mice has anxiolytic effects in tests of anxiety involving stimuli with positive incentive value (i.e. palatable food or a novel conspecific mouse). We also found that this anxiolytic effect is mediated, at least in part, by ghrelin receptors in the ventral tegmental area. A role for ghrelin in social anxiety is particularly intriguing because social withdrawal and social anxiety are common symptoms of depression and there is strong evidence that ghrelin has other antidepressant properties. Depressive-like behaviors can be generated in mice by psychosocial stressors such as chronic social defeat. Thus we explored the possibility that treatment with the ghrelin agonist GHRP6 could prevent and/or alleviate stress-induced social anxiety when administered alone or in combination with the commonly prescribed antidepressant citalopram. We found that peripheral GHRP6 treatment was not sufficient to prevent or treat social withdrawal induced by chronic stress exposure. Chronic GHRP6 treatment, however, increased the number of immature neurons in the hippocampus.Furthermore, we found that chronic GHRP6 treatment reduced weight gain when administered alone as well as in combination with citalopram. Weight gain is a common side effect of antidepressant treatment thus the finding that GHRP6 can reduce these metabolic side effects has potential therapeutic potential.3.