Role of brain melanocortin receptor 5 in physical activity in rats

Abstract

The brain melanocortin (MC) system is one of several systems that regulate energy balance; it consists of peptides such as α‐MSH that act via MC receptors (MCR). Brain MC3R and MC4R are known to modulate energy expenditure and food intake; little is known about the role of MC5R in the brain, however. We previously demonstrated that, compared to low‐activity rats, high‐activity rats show enhanced MC5R mRNA expression in the peri‐fornical lateral hypothalamus (PeFLH) but not in the paraventricular nucleus (PVN). To test the hypothesis that hypothalamic MC5R expression is related to enhanced physical activity (PA), we stereotaxically implanted guide cannulae in male Sprague‐Dawley rats, then measured the ability of a novel MC5R‐specific agonist in the PVN and PeFLH to increase PA. Intra‐PeFLH microinjections significantly enhanced PA in a dose‐dependent manner, while no such effect was seen in the PVN. The MC5R agonist (compared to vehicle) did not significantly suppress food intake in either of the hypothalamic regions, however. Thus, specific, regional activation of brain MC receptors could affect different aspects of energy balance, particularly PA. We will now investigate if these site‐ and receptor subtype‐specific MC differences may underlie individual differences in daily PA. MC5R agonist was obtained from M. Bednarek (MedImmune Ltd, Cambridge, UK). Research support was from NIH R01NS055859 to CMN and AHA11PRE7320029 to CS.