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

Ghrelin, a gut-derived peptide, is associated with feeding, energy balance, reward and the stress response. Among many of its functions, the role of ghrelin in anxiety has been particularly controversial. Here, we demonstrated that increasing ghrelin receptor activity (particularly in the VTA) in mice has anxiolytic effects in tests involving stimuli with positive incentive value (i.e. palatable food or social opportunity). A role for ghrelin in social anxiety is intriguing because social anxiety is a common symptom of depression. Thus, we explored the possibility whether treatment with ghrelin agonist GHRP6 alone of in combination with SSRI citalopram could prevent and/or alleviate stress-induced social anxiety. We found that peripheral GHRP6 treatment was not sufficient to prevent/treat stress-induced social anxiety. Interestingly, post stress GHRP6 and GHRP6+citalopram treatment reduced weight gain, a common side effect of antidepressant treatment. Thus, our finding that GHRP6 can reduce these metabolic side effects has potential therapeutic potential.