| First Author | Cui H | Year | 2013 |
| Journal | Genes Brain Behav | Volume | 12 |
| Issue | 6 | Pages | 658-65 |
| PubMed ID | 23786641 | Mgi Jnum | J:213389 |
| Mgi Id | MGI:5584260 | Doi | 10.1111/gbb.12057 |
| Citation | Cui H, et al. (2013) The expression of MC4Rs in D1R neurons regulates food intake and locomotor sensitization to cocaine. Genes Brain Behav 12(6):658-65 |
| abstractText | 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. |
