Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context

Abstract

We recently demonstrated that vasopressin (AVP) in the lateral septum modulates social play behavior differently in male and female juvenile rats. However, the extent to which different social contexts (i.e., exposure to an unfamiliar play partner in different environments) affect the regulation of social play remains largely unknown. Given that AVP and the closely related neuropeptide oxytocin (OXT) modulate social behavior as well as anxiety-like behavior, we hypothesized that these neuropeptides may regulate social play behavior differently in novel (novel cage) as opposed to familiar (home cage) social environments. Administration of the specific AVP V1a receptor (V1aR) antagonist (CH2)5Tyr(Me2)AVP into the lateral septum enhanced home cage social play behavior in males but reduced it in females, confirming our previous findings. These effects were context-specific because V1aR blockade did not alter novel cage social play behavior in either sex. Furthermore, social play in females was reduced by AVP in the novel cage and by OXT in the home cage. Additionally, females administered the specific OXT receptor antagonist desGly-NH2,d(CH2)5−[Tyr(Me)2,Thr4]OVT showed less social play in the novel as compared to the home cage. AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze), but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms. Moreover, none of the other drug treatments that altered social play had an effect on anxiety, suggesting that these drug-induced behavioral alterations are relatively specific to social behavior. Overall, we showed that AVP and OXT systems in the lateral septum modulate social play in juvenile rats in neuropeptide-, sex- and social context-specific ways. These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior.

A working model for the assessment of disruptions in social behavior among aged rats: The role of sex differences, social recognition, and sensorimotor processes

“…The vast majority of rodent studies examining social behavior have done so in young rodents, during early developmental periods in which social behavior often manifests as rough-and-tumble play (Panksepp et al, 1984; Bredewold et al, 2014; van Kerkhof et al, 2013; Kummer et al, 2011; Pellis et al, 1997; Smith, 2012; Strickland and Smith, 2015; Trezza et al, 2011; Vanderschuren and Trezza, 2014; Veenema et al, 2012; Yates et al, 2013; Zakharova et al, 2009; Zernig and Pinheiro, 2015). Indeed, social processes in young rodents are richly expressed at high levels and lend themselves toward ready delineation of neural substrates underlying social play behavior.…”

Sex differences in sensitivity to the social consequences of acute ethanol and social drinking during adolescence

“…Furthermore, the endogenous cannabinoid system is implicated in ethanol intake and reinforcement (Vengeliene et al, 2008), suggesting that this system might be activated differentially by ethanol in adolescent males relative to their female counterparts. There is also some experimental evidence that social neuropeptides, vasopressin and oxytocin, playing a substantial role in regulation of social behavior during adulthood (Veenema and Neumann, 2008), are sex-dependently involved in modulation of play fighting (Bredewold et al, 2014; Veenema et al, 2013). Given that these neuropeptide systems are sensitive to ethanol (McGregor and Bowen, 2012), they may contribute to observed sex differences in sensitivity to ethanol-associated facilitation and inhibition of play fighting as well.…”

Behavioral and mechanistic insight into rodent empathy

“…Conversely, chronic intranasal oxytocin treatment produced a selective reduction of social behaviors concomitant with a reduction of oxytocin receptors throughout the brain (Huang et al, 2014). In addition, social context is another factor known to alter the behavioral responses of oxytocin, where social play is dependent on oxytocin in novel but not familiar environments (Bredewold et al, 2014). Interestingly, in male rats the intranasal administration of oxytocin limited proactive aggression and increased social exploration of a male resident towards an unfamiliar male intruder (Calcagnoli et al, 2015), which is not in perfect agreement with the promotion of out-group aggression in people (De Dreu et al, 2010).…”