Downregulation of melanocortin receptors in brain areas involved in food intake and reward mechanisms in obese (OLETF) rats.
The melanocortin (MC)4 receptor is important for food intake and weight homeostasis as it mediates the orexigenic and anorexigenic effects of the MCs. OLETF (Otsuka-Long-Evans-Tokushima-Fatty) rats are a selective inbred strain of polygenic variant rats which overeat and develop obesity with elevated leptin levels. We investigated by autoradiography if the expression of MC receptors were altered in ovariectomized estradiol-replaced female OLETF rats compared to their controls (Long-Evans-Tokushima-Otsuka (LETO) rats). We found that OLETF rats show a reduction in total [125I]NDP-MSH MC receptor binding in the ventromedial hypothalamic nucleus, perhaps reflecting an increased release of MC peptides in this region. The levels of MC receptors in the arcuate nucleus and the paraventricular hypothalamic nucleus were not changed. Interestingly, the OLETF rats also showed reduced MC-receptor binding in areas such as the nucleus accumbens shell, and the ventral tegmental area, both of which are believed to be involved in reward systems. Similarities in the changes of MC receptor expression in obese animals and in animals treated with opiates may suggest a neurobiological link between food intake mediated through the MC receptors and reward.
Lindblom
J
J
Department of Pharmaceutical Biosciences, Uppsala University, Sweden. jonas.lindblom@farmbio.uu.se
Schiöth
H B
HB
Watanobe
H
H
Suda
T
T
Wikberg
J E
JE
Bergström
L
L
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D015536:Down-Regulation; D004435:Eating / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D020738:Leptin / Q000097:blood; D009765:Obesity / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D020334:Rats, Inbred OLETF; D011919:Rats, Inbred Strains; D018043:Receptors, Corticotropin / Q000378:metabolism*; D044101:Receptors, Melanocortin; D012201:Reward; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism
D020738:Leptin; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D004958:Estradiol