It is well established that the nonapeptide oxytocin (Oxt) is important for the neural modulation of behaviors in many mammalian species. Since its discovery in 1906 and synthesis in the early 1950s, elegant pharmacological work has helped identify specific neural substrates on which Oxt exerts its effects. More recently, mice with targeted genetic disruptions of the Oxt system-i.e., both the peptide and its receptor (the Oxtr)-have further defined Oxt's actions and laid some important scientific groundwork for studies in other species. In this article, we highlight the scientific contributions that various mouse knockouts of the Oxt system have made to our understanding of Oxt's modulation of behavior. We specifically focus on how the use of these mice has shed light on our understanding of social recognition memory, maternal behavior, aggression, and several nonsocial behaviors. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 190-201, 2017.

The arginine vasopressin 1b receptor (Avpr1b) is involved in the modulation of a variety of behaviors and is an important part of the mammalian hormonal stress axis. The Avpr1b is prominent in hippocampal CA2 pyramidal cells and in the anterior pituitary corticotrophs. Decades of research on this receptor has demonstrated its importance to the modulation of social recognition memory, social forms of aggression, and modulation of the hypothalamic-pituitary-adrenal axis, particularly under conditions of acute stress. Further, work in humans suggests that the Avpr1b may play a role in human neuropsychiatric disorders and its modulation may have therapeutic potential. This paper reviews what is known about the role of the Avpr1b in the context of social behaviors, the stress axis, and human neuropsychiatric disorders. Further, possible mechanisms for how Avpr1b activation within the hippocampus vs. Avpr1b activation within anterior pituitary may interact with one another to affect behavioral output are proposed.

| 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.

Arginine vasopressin (AVP) is a neuropeptide which acts centrally to modulate numerous social behaviors. One receptor subtype through which these effects occur is the AVP 1a receptor (AVPR1A). The modulatory effects of Avp via the AVPR1A varies by species as well as sex, since both AVP and the AVPR1A tend to be expressed more prominently in males. Beyond these neuromodulatory effects there are also indications that the AVP system may play a role in early development to, in part, organize sex‐specific neural circuitry that is important to sexually dimorphic social behaviors in adulthood. However, to date, AVP's role in early development is poorly understood, particularly with respect to its differential effect on males and females. In order to determine the timing and distribution of the AVP system in early brain development, we examined the brains of male and female C57BL/6J mice between embryonic day (E) 12.5 and postnatal day (P) 2 and quantified Avp and Avpr1a mRNA using qPCR and AVPR1A protein using receptor autoradiography. The mRNA for Avp was measurable in males and females starting at E14.5, with males producing more than females, while Avpr1a mRNA was found as early as E12.5, with no difference in expression between sexes. AVPR1A binding was observed in both sexes starting at E16.5, and while there were no observed sex differences, binding density and the number of neuroanatomical areas did increase over time. These data are significant as they provide the first whole‐brain characterization of the vasopressin system in the embryonic mouse. Further, these findings are consistent with data from other species, that have documented a sex difference in the vasopressin system during early brain formation.

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