Activation patterns of vasopressinergic and oxytocinergic brain regions following social play exposure in juvenile male and female rats

Abstract

Social play is a highly rewarding and motivated behavior predominately displayed by juveniles and expressed by nearly all mammalian species. Prior work suggested that the vasopressin (AVP) and oxytocin (OT) systems can regulate the expression of social play in sex-specific ways. Here we investigated whether there are sex differences in the recruitment of vasopressinergic and oxytocinergic brain regions following social play exposure in juvenile rats. Single-housed rats were allowed to play, in their home cage, with an age- and sex-matched unfamiliar conspecific for 10 min, or received similar handling but no partner. Double-labeled fluorescent immunohistochemistry for Fos and either AVP or OT was completed in adjacent series of tissue to determine recruitment of AVP- and OT-immunoreactive neurons in response to social play. Exposure to social play did not increase recruitment of AVP or OT neurons in the supraoptic (SO) or paraventricular (PVH) hypothalamic nuclei of either sex compared to the no-play control condition. Interestingly, there was a robust sex difference in SO recruitment, irrespective of social play condition, with males exhibiting twice the recruitment of SO-AVP and SO-OT neurons compared to females. Lastly, exposure to social play increased recruitment of the posterior bed nuclei of the stria terminalis (pBST) and the posterodorsal medial amygdalar nucleus (MEApd) compared to the no-play control condition, and this effect was most pronounced in females. Our findings revealed sex differences in the recruitment of brain regions (i) independent of play condition (i.e., SO) possibly representing a sex difference in the baseline levels of AVP and OT signaling required for typical functioning and (ii) specific to play condition (i.e., pBST, MEApd). In sum, this study provides further evidence that the neural substrates underlying social play behavior are sex-specific. This article is protected by copyright. All rights reserved.

Microglia Sculpt Sex Differences in Social Behavior

“…This seems likely, however, given that the medial amygdala is known to regulate social play and sends projections to other brain regions that support social play, such as the lateral septum. Indeed, a previous study also observed higher immediate early gene activation in the medial amygdala during social play, albeit more so in females than in males (Reppucci et al, 2018).…”

Wistar rats and C57BL/6J mice differ in their motivation to seek social interaction versus food in the Social versus Food Preference Test

“…Lastly, while sex differences in the current set of behavioral experiments were minimal, we would encourage the continued use of both sexes in future investigations of the neural substrates underlying social versus food preference [52,53]. This is critical because an absence of sex differences in behavior could still be caused by sex differences in its neural underpinnings [54], and we and others have demonstrated that the neural mechanisms underlying motivated social behavior can differ in males and females [34,[55][56][57][58][59][60].…”

Involvement of orexin/hypocretin in the expression of social play behaviour in juvenile rats

“…Each image represented a sampling area that measured 433.45 µm x 330.25 µm. The number of double-labelled neurons [ORX-immunoreactive (-ir) + Fos-ir], the total number of ORX-ir neurons, and the total number of Fos-ir nuclei were counted as previously described (Petrovich, Hobin, & Reppucci, 2012;Reppucci, et al, 2018) and then averaged for each of the three sampling locations. The percent of ORX neurons that were co-labelled with Fos was quantified as: (# double-labelled neurons/total number of ORX-ir neurons)*100.…”

“…The frequency of stereotypical play behaviours was analysed as previously described (Veenema, et al, 2013). Nape attacks and pins are considered to be measures of social play motivation (appetitive and consummatory, respectively), while supine positions considered an indication of social play receptivity (Ikemoto and Panksepp, 1992;Panksepp and Beatty, 1980;Vanderschuren, et al, 1997), and are less frequently expressed by experimental rats in our testing paradigm (Bredewold, et al, 2018;Bredewold, et al, 2015;Bredewold, et al, 2014;Reppucci, et al, 2018;Veenema, et al, 2013). Supplemental Table 1.…”

“…We assessed the role of the ORX system in regulating social play in both male and female juvenile rats, because previous studies demonstrated sex-specific regulation of social play behaviour by other neuropeptides (Bredewold et al, 2018;Bredewold, Schiavo, van der Hart, Verreij, & Veenema, 2015;Bredewold, Smith, Dumais, & Veenema, 2014;Paul et al, 2014;Reppucci, Gergely, & Veenema, 2018;Veenema, Bredewold, & de Vries, 2013). We first examined whether juvenile rats exposed to social play had greater recruitment of ORX-A neurons than those not exposed to social play.…”