Comparison of the distribution of oxytocin and vasopressin 1a receptors in rodents reveals conserved and derived patterns of nonapeptide evolution

Abstract

| INTRODUC TI ONOxytocin (OT) and vasopressin (VP) are important factors for both peripheral physiological functions, 1-6 and the central regulation of a variety of behaviours. [7][8][9][10][11] OT and VP modulate several behaviours important for the survival and propagation of species, including parental behaviour, 12-14 reproduction 15-18 and behaviours important for other social interactions. 19,20 These peptides (and their non-mammalian homologues; hereafter referred to as OT and VP for simplicity) have been found to influence social behaviour in one form AbstractOxytocin (OT) and vasopressin (VP) are known modulators of social behaviour across rodents. Research has revealed the location of action of these nonapeptides through localization of their associated receptors, which include the oxytocin receptor (OTR) and the vasopressin 1a receptor (V1aR). As research into these complex systems has progressed, studies investigating how these systems modulate behaviour have remained relatively narrow in scope (ie, focused on how a single brain region shapes behaviour in only a handful of species). However, the brain regions that regulate social behaviour are part of interconnected neural networks for which coordinated activity enables behavioural variation. Thus, to better understand how nonapeptide systems have evolved under different selective pressures among rodent species, we conducted a meta-analysis using a multivariate comparative method to examine the patterns of OTR and V1aR density expression in this taxon. Several brain regions were highly correlated based on their OTR and V1aR binding patterns across species, supporting the notion that the distribution of these receptors is highly conserved in rodents. However, our results also revealed that specific patterns of V1aR density differed from OTR density, and within-genus variance for V1aR was low compared to between-genus variance, suggesting that these systems have responded and evolved quite differently to selective pressures over evolutionary time. We propose that, in addition to examining single brain regions of interest, taking a broad comparative approach when studying the OT and VP systems is important for understanding how the systemic action of nonapeptides modulate social behaviour across species. K E Y W O R D S evolutionary plasticity, receptor autoradiography, Rodentia, social behaviour network S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Freeman AR, Aulino EA, Caldwell HK, Ophir AG. Comparison of the distribution of oxytocin and vasopressin 1a receptors in rodents reveals conserved and derived patterns of nonapeptide evolution. J Neuroendocrinol.

Neural correlates of mating system diversity: oxytocin and vasopressin receptor distributions in monogamous and non-monogamous Eulemur

“…In Eulemur, we observed strong AVPR1a binding, but diffuse or modest OXTR binding, in both the striatum and hippocampal regions. This striatal pattern is comparable to that seen in coppery titi monkeys 47 , but it contrasts with the dense OXTR expression found in both rodents 67 and marmosets 57 . Hippocampal patterns in Eulemur are reversed from that observed in titi monkeys 47 .…”

Oxytocin receptors are widely distributed in the prairie vole (Microtus ochrogaster) brain: Relation to social behavior, genetic polymorphisms, and the dopamine system

“…Young & Wang, 2004). Subsequent studies in rodents and primates have supported the idea that interspecies variation in social behavior results from variation in OXTR distribution (Campbell et al., 2009; Francis et al., 2000; A. R. Freeman et al., 2020; S. M. Freeman & Young, 2016; Rogers Flattery et al., 2021; Smeltzer et al., 2006). A recent quantitative analysis of data from 13 rodent species compared in seven papers demonstrates that OXTR density in the NAc and lateral septum predicts social group size, behavior toward conspecifics, and reproductive strategies (Olazábal & Sandberg, 2020).…”

“…Young & Wang, 2004). Subsequent studies in rodents and primates have supported the idea that interspecies variation in social behavior results from variation in OXTR distribution (Campbell et al, 2009;Francis et al, 2000;A. R. Freeman et al, 2020; S. M. Freeman & Young, 2016;Rogers Flattery et al, 2021;Smeltzer et al, 2006).…”

Binding affinities of oxytocin, vasopressin and Manning compound at oxytocin and V1a receptors in male Syrian hamster brains

“…The use of diverse animal models, each with its own unique constellation of social behavior, provides a comprehensive yet complex view of the roles of OT and AVP in modulating social behavior 8 . A recent comparative analysis shows that, with respect to receptor distribution, OTR and V1aR are quite variable within Rodentia 9 . Even among closely related species, there are differences in the OTR and V1aR amino acid sequences, which may translate to differences in ligand binding and signaling.…”