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.