Effects of oxytocin receptor antagonism on social function and corticosterone release after adolescent social instability in male rats

Abstract

Oxytocin influences social behaviour and hypothalamic-pituitary-adrenal (HPA) function. We previously found that social instability stress (SS) from postnatal day 30 to 45 increased oxytocin receptor (OTR) densities in the lateral septum and nucleus accumbens of adolescent male rats. Here, we investigated social behaviour and HPA function in adolescent male SS rats compared with age- and sex-matched controls after intraperitoneal treatment with an OTR antagonist L-368,899 (OTR-A). Regardless of OTR antagonism, adolescent SS rats spent more time in social approach (investigation through wire mesh) but less time in social interaction (physical interaction) with unfamiliar same-sex and same-age peers than did controls. However, OTR-A-treatment caused SS rats to be more socially avoidant than OTR-A-treated controls and saline-treated rats of the same condition. Additionally, the predicted rise in plasma corticosterone in response to OTR-A treatment was blunted in SS rats. Fos immunoreactivity (IR) was used as a marker of neural activation in social brain regions and oxytocin-IR was examined in the paraventricular nucleus of the hypothalamus (PVN) in response to interacting with unfamiliar peers in SS and control rats after OTR-A treatment. OTR-A treatment had little effect on Fos-IR and oxytocin-IR in the analyzed brain regions, but SS rats had lower Fos-IR and oxytocin-IR in the PVN and greater Fos-IR in subregions of the prefrontal cortex, and hippocampus, and lateral septum than did controls. Finally, binding density of OTR was measured in the PVN and hippocampus, and greater OTR binding density was found in the PVN of SS rats. Together, these data demonstrate a greater influence of OTR antagonism on social behaviour and a reduced influence of OTR antagonism on HPA responses after adolescent SS in male rats. The results also suggest that differences in neural functioning in the prefrontal cortex, hippocampus and lateral septum of adolescent SS rats may be involved in their altered social behaviour relative to that of controls.