INVESTIGADORES
RUBINSTEIN marcelo
congresos y reuniones científicas
Título:
Neuronal dopamine D2 receptors promote aggressive and territorial behaviors
Autor/es:
NOAIN D; DIEGO M. GELMAN; BELLO-GAY E; PEPER M; GARCÍA-TORNADÚ I; PÉREZ MILLÁN, MI; BECU-VILLALOBOS D; LOW MJ; RUBINSTEIN M
Lugar:
Chicago, IL, EEUU
Reunión:
Congreso; 40th Annual Meeting of the Society for Neuroscience; 2009
Institución organizadora:
Society for Neuroscience
Resumen:
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 levelsindicating 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.