Ghrelin receptors in the VTA mediate stress induced changes in caloric intake during chronic social defeat

Su-Bin Park (2015)S.B. Park, T. Rodrigues, C. Wallace, K. Mezher, L. Hyland, M. Klein, A. Edwards, Z.R. Patterson, H. MacKay, A. Abizaid

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Ghrelin, a gut-derived peptide hormone, is associated with feeding, energy balance, and the stress response. Exposure to stressors lead to elevated plasma levels of ghrelin, and these are associated with metabolic changes generated to meet the demands of the stressor. In mice, exposure to chronic social defeat leads to increases in caloric intake, and in particular, the intake of carbohydrate rich diets, and these effects are mediated in part by increased ghrelin secretion. It is not, however, the site at which ghrelin acts to mediate this effect. To determine this, we examined differences in the expression of the ghrelin receptor (GHSR) in regions of the brain that are associated with food intake, and the stress response including the ventral portion of the hypothalamus (vHYP), ventral tegmental area (VTA), prefrontal cortex (PFC), and the hippocampus (HIPP). As expected, exposure to chronic social defeat resulted in elevated plasma ghrelin level (p. < 0.05), and significant changes in GHSR mRNA expression that were site dependent. Of these, the VTA was the only region where GHSR mRNA expression was significantly elevated (p. < 0.05). To examine the relevance of elevated GHSR expression in the VTA, we conducted an experiment where animals received a GHSR antagonist (JMV2959) or vehicle chronically infused into the VTA via cannula attached to the osmotic minipump while being stressed. Stressed mice treated with JMV2959 showed attenuated intake of the carbohydrate rich diet compared to stressed animals receiving vehicle, suggesting that GHSR in the VTA is important for the increase in carbohydrate intake during chronic social defeat.