Sexual Differentiation of Social Play in Rat Pups Is Mediated by the Neonatal Androgen-Receptor System

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Abstract
Social play in juvenile rats, like that in several primate species (including humans), is sexually dimorphic. Males initiate and become involved in more play-fights than do their female peers. The play-fighting of female pups can be masculinized by neonatal exposure to either testosterone or 5α-dihydrotestosterone, suggesting that in the rat the masculinization of social play is mediated by the androgen-receptor system. In this paper we present evidence that further supports this hypothesis. In the first study we found that male pups treated with the antiandrogen, flutamide, during the neonatal period (days 1 through 10 of life) engaged in less play-fighting than did control males. Moreover, flutamide-treated, male pups play-fought no more frequently than did untreated females. In a subsequent study we found that flutamide, which blocked the masculinization of social play, dramatically reduced a testosterone-induced translocation of androgen receptors to the nuclear compartment in various brain regions (as measured by a nuclear exchange assay) in neonates. In a final study we examined the play-fighting of juvenile rat pups bearing the testicular feminization mutation (Tfm); animals that are known to be insensitive to androgens and show a marked deficiency of androgen receptors. Tfm males engaged in significantly less play-fighting than did control males. The Tfm males, like the flutamide-treated males, engaged in play-fighting at rates that were comparable to those of females. Taken together with previous data these findings strongly suggest that the sexual differentiation of social play in juvenile rats is mediated by the androgen-receptor system during the neonatal period.