Abstract

Oxytocin (OT) and vasopressin (AVP) regulate various social behaviors via activation of the OT receptor (OTR) and the AVP V1a receptor (V1aR) in the brain. Social behavior often differs across development and between the sexes, yet our understanding of age and sex differences in brain OTR and V1aR binding remains incomplete. Here, we provide an extensive analysis of OTR and V1aR binding density throughout the brain in juvenile and adult male and female rats, with a focus on regions within the social decision-making network. OTR and V1aR binding density were higher in juveniles than in adults in regions associated with reward and socio-spatial memory and higher in adults than in juveniles in key regions of the social decision-making network and in cortical regions. We discuss possible implications of these shifts in OTR and V1aR binding density for the age-specific regulation of social behavior. Furthermore, sex differences in OTR and V1aR binding density were less numerous than age differences. The direction of these sex differences was region-specific for OTR but consistently higher in females than in males for V1aR. Finally, almost all sex differences in OTR and V1aR binding density were already present in juveniles and occurred in regions with denser binding in adults compared to juveniles. Possible implications of these sex differences for the sex-specific regulation of behavior, as well potential underlying mechanisms, are discussed. Overall, these findings provide an important framework for testing age- and sex-specific roles of OTR and V1aR in the regulation of social behavior.

Highlights

  • Oxytocin (OT) and vasopressin (AVP) are neuropeptides primarily synthesized in the paraventricular and supraoptic nuclei of the hypothalamus

  • OT receptor (OTR) and V1a receptor (V1aR) binding density were higher in juveniles than in adults in regions associated with reward and socio-spatial memory and higher in adults than in juveniles in key regions of the social decision-making network and in cortical regions

  • OTR binding density was significantly higher in juveniles than in adults in 15 brain regions, consisting of subregions in the olfactory nucleus, striatum, hypothalamus, amygdala, septum, hippocampus, and thalamus (Fig. 3a)

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Summary

Introduction

Oxytocin (OT) and vasopressin (AVP) are neuropeptides primarily synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. These OT and AVP-synthesizing nuclei send fiber projections to a wide array of brain regions (Buijs 1978, 1980; Knobloch and Grinevich 2014; Rood and De Vries 2011) Via these direct projections, as well as via dendritic release (Ludwig et al 2002, 2005; Ludwig and Leng 2006), OT and AVP reach the OT receptor (OTR) and V1a receptor (V1aR), which are widely distributed in the brain (Gimpl and Fahrenholz 2001; Tribollet et al 1990, 1998; Shapiro and Insel 1989; Dumais et al 2013; Dumais and Veenema 2016a). Such age differences in the regulation of social behavior by AVP, and possibly OT, may be due to age differences in OTR and V1aR expression in the brain

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