“Neuronal dopamine D2 receptors promote aggressive and territorial behaviors between male mice.”

NOAÍN, D; GELMAN, D; BELLO GAY, E; PEPER, M; GARCÍA-TORNADÚ, I; PÉREZ-MILLÁN, MI; BECÚ, D; LOW, MJ; RUBINSTEIN, M

Chicago, Illinois, U.S

Congreso; 40th Annual Meeting of the Society for Neuroscience; 2009

Society for Neuroscience

Besides being involved in locomotor activity, cognition and reward, the dopamine D2 receptor (D2R) plays an important role in the regulation of the growth hormone (GH) axis and determination of normal body size. Our recent studies have showed that D2R deficient mice have fewer pituitary somatotropes and reduced GH levels and, as a consequence, are dwarfs. GH axis impairment in D2R deficient mice could be due to the lack of D2Rs in pituitary cells or in hypothalamic neurons that control pituitary function. In an effort to solve this question we generated a conditional mutant mouse strain carrying Drd2 null-alleles only in neurons of the nervous system. Homozygous mutant mice carrying two loxP sites flanking exon 2 of Drd2 (Drd2flox/flox) are indistinguishable from their wild-type siblings. To delete Drd2 functional alleles specifically from neurons, Drd2flox/flox mice were crossed with nestin-Cre transgenic mice. Compound Drd2flox/flox. Tg (nestin-Cre) mice lack Drd2 expression in all brain areas while retaining normal expression levels in pituitary lactotropes and melanotropes. Mice carrying neuronal Drd2 null alleles (nDrd2-/-) displayed decreased weight and length curves together with reduced GH pituitary content and IGF-1 plasmatic levels indicating that D2Rs involved in the maturation of the GH axis are localized in neurons. Interestingly, hypothalamic expression of growth hormone releasing hormone (GHRH) was reduced in nDrd2-/- mice probably due to the lack of D2R stimulation on somatosatin neurons. Male nDrd2-/- mice have normal levels of testosterone but largely reduced levels of major urinary proteins (MUPs). Interestingly, urine of male nDrd2-/- mice was unable to promote aggressive and territorial behavior in isolated wild-type mice when tested in a resident vs. intruder paradigm, a social interaction tube test and a territorial urine-marking test. In summary, neuronal inactivation of D2Rs revealed a novel function of this receptor in the development of secondary sexual features involved in social, aggressive and territorial behaviors between males that are key for reproductive success.