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

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.

Cognitive effects of endocrine-disrupting chemicals in animals.

“…The roles of these hypothalamic nuclei in reproductive behavior are not completely understood, but the VMN appears to be involved in the lordosis response in female rats (17), and the SDN-POA has been implicated in the execution of coital behavior in male rats (16). Some aspects of sexual differentiation of the brain, including the development of sexually dimorphic patterns of social play, appear to be regulated by the direct actions of androgens in the brain, rather than by the aromatization of androgens to estrogen (18). A similar process of sexual differentiation appears to occur in the brains of all mammalian species including humans.…”

Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague-Dawley rat.

“…Although estradiol is critical for masculinization of some behaviors in the perinatal rat, others are affected specifically by androgens during the neonatal period. Play is organized by the perinatal interaction of androgens with the AR (Meaney et al 1983;Meaney and McEwen 1986;Pellis and Pellis 1997). Although limited examples of androgen organization of behavior exist in the rat, it appears to be more common in the nonhuman primate (Cooke et al 1998;Hines 1992).…”

“…However, some behaviors, such as rough-and-tumble play, are specifically organized by androgens. The critical time in the rat for organization of play is the early neonatal period, when interactions of androgens with the AR set up the sex difference observed in juveniles (Meaney et al 1983;Meaney and McEwen 1986;Pellis and Pellis 1997). Studies have shown that increased male rough-and-tumble play is specifically organized by the stimulation of ARs in the amygdala region of the brain (Meaney et al 1983) and is not dependent on activational effects of steroids (Meaney and McEwen 1986).…”

“…The critical time in the rat for organization of play is the early neonatal period, when interactions of androgens with the AR set up the sex difference observed in juveniles (Meaney et al 1983;Meaney and McEwen 1986;Pellis and Pellis 1997). Studies have shown that increased male rough-and-tumble play is specifically organized by the stimulation of ARs in the amygdala region of the brain (Meaney et al 1983) and is not dependent on activational effects of steroids (Meaney and McEwen 1986). Further, androgen receptor dysfunctions such as testicular feminized mutant males, neonatal castration, and neonatal exposure to the androgen-receptor antagonist flutamide decrease the expression of play by juvenile males, whereas administration of estradiol agonists does not increase play in either male or female rats (Meaney and Stewart 1981).…”

The role of androgen receptors in the masculinization of brain and behavior: What we've learned from the testicular feminization mutation

“…Play fighting is decreased in male rats castrated at birth and its frequency begins to decline at the onset of puberty (Beatty et al, 1981;Meaney, 1988;Pellis and Pellis, 1990). Analysis of Tfm male rats suggests that ARs are involved in the development of play fighting behavior since, as juveniles, Tfm males show decreased play fighting behavior compared to wt males (Meaney et al, 1983;Meaney, 1988), although recent data suggest that this difference may depend on the testing paradigm (Field et al, 2006). Tfm males also fail to show the male-typical decline in playful attack with age, but like wt males they do show a decline in some aspects of playful defense, indicating that ARs are involved in some but not all aspects of play fighting (Field et al, 2006).…”