Dopaminergic regulation of food intake. Insights obtained from the dopamine receptor D2 knockout mouse

GARCIA-TORNADU I; LUQUE GM; PEREZ-MILLAN MI; RAMIREZ MC; RECOUVREUX V; ORNSTEIN AM; DIAZ-TORGA G; BECU-VILLALOBOS D

Food Intake: Regulation, Assessing and Controlling

Nova Science Publishers

Lugar: Hauppauge, New York; Año: 2011; p. 59 - 82

Dopamine D2 receptor (D2R) participation in prolactin regulation is well documented, but the role of D2Rs in the control of hormones and peptides involved in food intake and glucose metabolism has not been extensively studied. Dopamine regulates hunger and satiety by acting in specific hypothalamic areas, but the effects of dopamine on food intake have yielded conflicting results in the literature due to the different actions of dopamine on various hypothalamic nuclei, the involvement of multiple receptors, and different responses in food intake when administered systemically or locally into the hypothalamus. Studies using D2R knockout mice (Drd2-/-) put forward new insights into the role of the D2R in the regulation of food intake. In adult male and female Drd2-/- mice food intake per g BW is increased. In females disruption of the D2R produced two potentially anorexigenic events: an increase in serum and hypothalamic aMSH, and a decrease in hypothalamic orexin expression. The very high chronic prolactin levels, found in this sex and genotype, probably counterbalance these effects. In Drd2-/- males, on the other hand, hypothalamic orexins, and serum and hypothalamic aMSH were not modified, and therefore, moderate hyperprolactinemia may account for increased food intake. These results suggest a sexually dimorphic participation of the D2R in food intake regulation, probably secondary to its regulation of prolactin secretion. A negative modulation of D2Rs on aMSH release and a positive action on the hypothalamic expression of orexins is suggested, which may function to maintain food intake not far from equilibrium in the knockout mice. These results reveal a participation of multiple factors in D2R regulation of food intake, and are discussed in relation to the role of dopamine in food intake obtained in other studies. In humans, a reduction in D2Rs is associated with addictive behavior towards food or drugs, and individuals with low numbers of D2Rs may be more vulnerable to such behaviors including compulsive food intake. But, the involvement of dopamine in pathological eating and obesity is poorly understood. The evidence linking mutations of the D2R gene and obesity syndromes in humans is limited, and in general, loss of function mutations associate with overweight. Studies using the Drd2-/- mouse may help to clarify the mechanisms which link dopamine to food intake.