Progesterone impairs social recognition in male rats.

The influence of progesterone in the brain and on the behavior of females is fairly well understood. However, less is known about the effect of progesterone in the male system. In male rats, receptors for progesterone are present in virtually all vasopressin (AVP) immunoreactive cells in the bed nucleus of the stria terminalis (BST) and the medial amygdala (MeA). This colocalization functions to regulate AVP expression, as progesterone and/or progestin receptors (PR)s suppress AVP expression in these same extrahypothalamic regions in the brain. These data suggest that progesterone may influence AVP-dependent behavior. While AVP is implicated in numerous behavioral and physiological functions in rodents, AVP appears essential for social recognition of conspecifics. Therefore, we examined the effects of progesterone on social recognition. We report that progesterone plays an important role in modulating social recognition in the male brain, as progesterone treatment leads to a significant impairment of social recognition in male rats. Moreover, progesterone appears to act on PRs to impair social recognition, as progesterone impairment of social recognition is blocked by a PR antagonist, RU-486. Social recognition is also impaired by a specific progestin agonist, R5020. Interestingly, we show that progesterone does not interfere with either general memory or olfactory processes, suggesting that progesterone seems critically important to social recognition memory. These data provide strong evidence that physiological levels of progesterone can have an important impact on social behavior in male rats.

The nuclear receptor corepressor has organizational effects within the developing amygdala on juvenile social play and anxiety-like behavior.

Nuclear receptor function on DNA is regulated by the balanced recruitment of coregulatory complexes. Recruited proteins that increase gene expression are called coactivators, and those that decrease gene expression are called corepressors. Little is known about the role of corepressors, such as nuclear receptor corepressor (NCoR), on the organization of behavior. We used real-time PCR to show that NCoR mRNA levels are sexually dimorphic, that females express higher levels of NCoR mRNA within the developing amygdala and hypothalamus, and that NCoR mRNA levels are reduced by estradiol treatment. To investigate the functional role of NCoR on juvenile social behavior, we infused small interfering RNA targeted against NCoR within the developing rat amygdala and assessed the enduring impact on juvenile social play behavior, sociability, and anxiety-like behavior. As expected, control males exhibited higher levels of juvenile social play than control females. Reducing NCoR expression during development further increased juvenile play in males only. Interestingly, decreased NCoR expression within the developing amygdala had lasting effects on increasing juvenile anxiety-like behavior in males and females. These data suggest that the corepressor NCoR functions to blunt sex differences in juvenile play behavior, a sexually dimorphic and hormone-dependent behavior, and appears critical for appropriate anxiety-like behavior in juvenile males and females.

Mecp2 organizes juvenile social behavior in a sex-specific manner.

Methyl-CpG-binding protein 2 (MeCP2) binds methylated DNA and recruits corepressor proteins to modify chromatin and alter gene transcription. Mutations of the MECP2 gene can cause Rett syndrome, whereas subtle reductions of MeCP2 expression may be associated with male-dominated social and neurodevelopmental disorders. We report that transiently decreased amygdala Mecp2 expression during a sensitive period of brain sexual differentiation disrupts the organization of sex differences in juvenile social play behavior. Interestingly, neonatal treatment with Mecp2 small interfering RNA within the developing amygdala reduced juvenile social play behavior in males but not females. Reduced Mecp2 expression did not change juvenile sociability or anxiety-like behavior, suggesting that this disruption is associated with subtle behavioral modification. This suggests that Mecp2 may have an overlooked role in the organization of sexually dimorphic behaviors and that male juvenile behavior is particularly sensitive to Mecp2 disruption during this period of development.