Poster Presentation The International Congress of Neuroendocrinology 2014

The role of the melanocortin system in regulating food intake via reward pathways in the ventral tegmental area (VTA)  (#248)

Katherine A Banks 1 , Kylie E Beale 1 , Anne K McGavigan 1 , James Kinsey-Jones 1 , Miriam Sharman 1 , Stephen R Bloom 1 , Kevin G Murphy 1
  1. Imperial College London, London, UK, United Kingdom

Energy homeostasis is regulated by complex neuroendocrine mechanisms. Pleasure-reward signalling is evolutionarily important in reinforcing food seeking and ingestive behaviour. Dopaminergic neuronal cell bodies located in the ventral tegmental area (VTA) project to a number of related pleasure-reward brain areas including the nucleus accumbens, amygdala, ventral pallidum and prefrontal cortex. Central and peripheral endocrine regulators of appetite, including ghrelin, leptin and the orexins, have been shown to affect food intake via the VTA. This suggests a role for appetite-regulating hormones and neuropeptides in affecting motivational status for a food reward. Melanocortins are centrally derived peptides with a well characterised anorectic role in food intake and energy expenditure through hypothalamic signalling.  However, the role of melanocortins in pleasure-reward signalling is less well characterised. Here we demonstrate the acute feeding effects of centrally administered melanocortin receptor 3 and/or 4 (MC3R/MC4R) agonists into the VTA in rats. [Nle4,D-Phe7]-α-MSH (NDP-MSH), a non-selective MC4R/MC4R agonist, was administered into the VTA of rats either fasted overnight or fed ad libitum on a standard chow diet.  Food intake was significantly decreased in rats fed ad libitum versus saline injected controls, whereas food intake was not significantly altered in rats fasted overnight. Administration of THIQ, a selective MC4R agonist, into the VTA of rats also significantly decreased food intake in rats fed ad libitum but not in rats fasted overnight. Increased c-fos like immunoreactivity, a marker of neuronal activation, was observed in the VTA, nucleus accumbens and prefrontal cortex following administration of NDP-MSH into the VTA. These findings suggest MC4R mediated melanocortin signalling in the VTA is able to reduce food intake specifically in satiated rats.