Hypothalamic orexin, OX1, MSH and MCRs expression in dopaminergic D2R knockout mice.

GARCIA-TORNADU,I; DIAZ-TORGA G; RISSO,G.; SILVEYRA,P.; CATALDI,N.; RAMIREZ,M.C.; LOW,MJ; LIBERTUN, C.; BECU-VILLALOBOS, D.

NEUROPEPTIDES

Elsevier

Año: 2009 vol. 43 p. 267 - 274

0143-4179

In male and female dopamine receptor 2 (D2R) knockout mice food intake per animal is unaltered while food per g BW is increased. We wished to evaluate the effect of D2R disruption on different components of energy balance and food intake regulation. We determined hypothalamic orexin precursor (PPO) expression, its receptor OX1, serum leptin levels, hypothalamic leptin receptor (OBR), circulating and pituitary á MSH levels, as well as central MC3 and MC4 receptors in wildtype and D2R knockout mice (KO). Loss of D2R caused a marked increase in serum prolactin levels, to higher levels in females compared to male KO mice. On the other hand, it produced a female-specific increase in circulating áMSH, and hypothalamic áMSH content, while neurointermediate áMSH content was decreased in both sexes. No differences were found in hypothalamic MC3R and MC4R concentration. Hypothalamic PPO mRNA expression was significantly decreased only in female KOs, while OX1 mRNA was not different between genotypes.  Serum leptin levels were also similar in both genotypes. Our results show that in female and not in male mice disruption of the D2R produces two potentially anorexigenic events: an increase in serum and hypothalamic áMSH, and a decrease in hypothalamic orexin expression. High prolactin levels, which are orexigenic, probably counterbalance these effects, so that total food intake is not altered. In males, hypothalamic PPO, and serum or hypothalamic áMSH are not modified, but prolactin levels are not so high and food intake per animal is unaltered. These results suggest a participation of the D2R in food intake regulation, and show the complexity of the regulatory system which modulates food intake.