Sex-specific effects of neonatal progestin receptor antagonism on juvenile social play behavior in rats

R M Forbes-Lorman

doi:10.1186/s12993-021-00183-z

Abstract

Developing mammals are exposed to progesterone through several sources; however, the role of progesterone in early development is not well understood. Males express more progestin receptors (PRs) than females within several brain regions during early postnatal life, suggesting that PRs may be important for the organization of the sex differences in the brain and behavior. Indeed, previous studies showed cognitive impairments in male rats treated neonatally with a PR antagonist. In the present study, we examined the role of PRs in organizing juvenile behaviors. Social play behavior and social discrimination were examined in juvenile male and female rats that had been treated with CDB, a PR antagonist, during the first week of postnatal life. Interestingly, neonatal PR antagonism altered different juvenile behaviors in males and females. A transient disruption in PR signaling during development had no effect on social discrimination but increased play initiation and pins in females. These data suggest that PRs play an important role in the organization of sex differences in some social behaviors.

Highlights

While it is clear that testosterone and its metabolites play an important role in the organization of the male brain and behavior through their actions on androgen receptors and estrogen receptors [1], less is known about the role of progesterone acting upon progestin receptors (PRs) in the developing brain
We examined the organizational role of PRs on juvenile social discrimination and juvenile social play behavior by treating male and female rats with CDB, a specific PR antagonist, during the first week of postnatal life
Simple main effects indicate that the effect of CDB in females approached significance (p = 0.06), while there was no effect of CDB in males (p = 0.37)

Summary

Introduction

While it is clear that testosterone and its metabolites play an important role in the organization of the male brain and behavior through their actions on androgen receptors and estrogen receptors [1], less is known about the role of progesterone acting upon progestin receptors (PRs) in the developing brain.Developing mammals are exposed to progesterone, both from fetal and maternal sources (reviewed in [2, 3]). Males express PRs as early as embryonic day 20 in many brain areas [7] and express more PRs than females within several hypothalamic regions on postnatal day (PN) but not PN10 [8, 9]. This sex difference in PRs in the developing brain suggests that PRs are important for the organization of the sex differences in the brain. CDB-4124 is a PR antagonist with a low binding affinity for glucocorticoid receptors [13] that has been shown to affect forced swim immobility in adult mice [14]

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Conclusion