Comparing vasopressin and oxytocin fiber and receptor density patterns in the social behavior neural network: Implications for cross-system signaling

Abstract

Vasopressin (AVP) and oxytocin (OXT) regulate social behavior by binding to their canonical receptors, the vasopressin V1a receptor (V1aR) and oxytocin receptor (OTR), respectively. Recent studies suggest that these neuropeptides may also signal via each other's receptors. The extent to which such cross-system signaling occurs likely depends on anatomical overlap between AVP/OXT fibers and V1aR/OTR expression. By comparing AVP/OXT fiber densities with V1aR/OTR binding densities throughout the rat social behavior neural network (SBNN), we propose the potential for cross-system signaling in four regions: the medial amygdala (MeA), bed nucleus of the stria terminalis (BNSTp), medial preoptic area, and periaqueductal grey. We also discuss possible implications of corresponding sex (higher in males versus females) and age (higher in adults versus juveniles) differences in AVP fiber and OTR binding densities in the MeA and BNSTp. Overall, this review reveals the need to unravel the consequences of potential cross-system signaling between AVP and OXT systems in the SBNN for the regulation of social behavior.

Keywords: Bed nucleus of the stria terminalis; Cross-talk; Medial amygdala; Medial preoptic area; Oxytocin; Oxytocin receptor; Periaqueductal grey; Social behavior; V1a receptor; Vasopressin.

Figure 1.

Representative images of AVP-ir fibers, OXT-ir fibers, V1aR binding, and OTR binding in the regions of the adult male rat SBNN. Dashed outlines indicate region boundaries. Bregma distances are based on the Paxinos and Watson Rat Brain Atlas (2007).

Figure 2.

Overview of sex and age differences in AVP-ir and OXT-ir cells/fiber density (measured as cell number/pixels: DiBenedictis et al., 2017) and in OTR and V1aR binding density (measured as disintegrations per minute/milligram tissue: Smith et al., 2017) in nodes of the rat SBNN. Significant main effects of sex (M = males, F = females) and of age (J = juveniles, A = adults) are indicate with the symbol >. Significant sex*age interaction effects are denoted by the inclusion of the appropriate sex + age. Green boxes represent cortico-striatal regions; blue boxes represent hypothalamic regions; red box represents midbrain region.

Figure 3.

Robust male-biased sex differences in OTR and more limited female-biased sex differences in V1aR. (A) OTR binding density in the MeP is higher in males than in females and higher in adult males than in juvenile males (Smith et al., 2017). (B) V1aR binding density in the MeP is higher in females than in males (Sex effect: F_(1,43) = 13.4, p<0.001), in both juveniles and adults (Age effect: F_(1,43) = 0.31, p=0.58; Interaction effect: F_(1,43) = 0.06, p=0.80). (C) OTR binding density in the BNSTp is higher in males than in females and higher in adults than in juveniles (Smith et al., 2017). (D) V1aR binding density in the BNSTp does not differ with sex or age (Sex effect: F_(1,41) = 1.70, p=0.20; Age effect: F_(1,41) = 0.20, p=0.66; Interaction effect: F_(1,41) = 0.37, p=0.55). (E) Cohen’s D effect sizes for significant sex differences. Data presented in B and D was conducted according to Smith et al. (2017). *p<0.05, ^#p<0.05 versus respective juvenile group, 2-way ANOVA, values indicate means (disintegrations per minute /milligram tissue) + SEM.