MC4R regulates food intake and locomotor sensitization to cocaine

[Semin]

The expression of MC4Rs in D1R neurons regulates food intake and locomotor sensitization to cocaine.
2013

Abstract
While it is known that mice lacking melanocortin 4 receptor (MC4R) expression develop hyperphagia resulting in early-onset obesity, the specific neural circuits that mediate this process remain unclear. Here, we report that selective restoration of MC4R expression within dopamine-1 receptor-expressing neurons [MC4R/dopamine 1 receptor (D1R) mice] partially blunts the severe obesity seen in MC4R-null mice by decreasing meal size, but not meal frequency, in the dark cycle. We also report that both acute cocaine-induced anorexia and the development of locomotor sensitization to repeated administration of cocaine are blunted in MC4R-null mice and normalized in MC4R/D1R mice. Neuronal retrograde tracing identifies the lateral hypothalamic area as the primary target of MC4R-expressing neurons in the nucleus accumbens. Biochemical studies in the ventral striatum show that phosphorylation of DARPP-32(Thr) (-34) and GluR1(Ser) (-845) is diminished in MC4R-null mice after chronic cocaine administration but rescued in MC4R/D1R mice. These findings highlight a physiological role of MC4R-mediated signaling within D1R neurons in the long-term regulation of energy balance and behavioral responses to cocaine.
PMID]

[Atomic Man]

Thanks for posting this study! It may be worth noting, in this connection, that Palatin Technologies is developing a melanocortin-4 receptor peptide to treat obesity. But it seems to me that users of Melanotan-II and PT-141 already experience a reduced appetite, at least this is what my survey results show so far; so even those peptides may be contributing, in some way, toward weight loss. (The scientific term is energy homeostasis, and the melanocortins are definitely involved in that.) One respondent said he can comfortably go 24 hours without eating when using PT-141.

[uchihasasuke]

Yes, I've also read this somewhere on the internet that melanocortin can improve the metabolism of obese mice that were diet induced. Hopefully, they will further advance in applying this to humans.