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Review
. 2018 Oct:51:14-24.
doi: 10.1016/j.yfrne.2017.10.004. Epub 2017 Oct 18.

Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery

Zhimin Song  1 , H Elliott Albers  2
Affiliations
Review

Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery

Zhimin Song et al. Front Neuroendocrinol. 2018 Oct.

Abstract

Oxytocin (OT) and arginine-vasopressin (AVP) act in the brain to regulate social cognition/social behavior and in the periphery to influence a variety of physiological processes. Although the chemical structures of OT and AVP as well as their receptors are quite similar, OT and AVP can have distinct or even opposing actions. Here, we review the increasing body of evidence that exogenously administered and endogenously released OT and AVP can activate each other's canonical receptors (i.e., cross-talk) and examine the possibility that receptor cross-talk following the synaptic and non-synaptic release of OT and AVP contributes to their distinct roles in the brain and periphery. Understanding the consequences of cross-talk between OT and AVP receptors will be important in identifying how these peptides control social cognition and behavior and for the development of drugs to treat a variety of psychiatric disorders.

Keywords: Autism spectrum disorder; G protein-coupled receptors; Intranasal administration; Pair bonding; Prosocial behavior; Social behavior; Social cognition; Social communication; Social recognition; Social reward.

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Figures

Figure 1
Figure 1
Schematic diagram of the primary structure of oxytocin and arginine-vasopressin. Seven of the nine amino acid sequences of these peptides are identical. Amino acids in the third and eighth positions differ (in red). Both peptides contain disulphide bridges between Cysteine (Cys) residues at positions one and six.
Figure 2
Figure 2
Diagrammatic representations of the oxytocin- (OT) and arginine-vasopressin- containing (AVP) neural network in rodents. It is noteworthy that OT and AVP immunoreactivity can vary by species, sex, age and social experience [8; 127]. These diagrams represent a compilation of the major OT and AVP projections from several rodent species. In addition to the cell bodies indicated in the diagram there are also accessory nuclei that likely also play an important role. A. OT network: [97; 128; 129; 130; 131; 132]. B. AVP network: [97; 114; 131; 133; 134; 135; 136] Abbreviations: Amygdala (AMY), Bed nucleus of the stria terminalis (BST), Caudate-putamen (CPU), Cingulate cortex (CC), Dorsal raphe (DR), Hippocampus (HPC), Lateral septum (LS), Locus coeruleus (LC), Medial preoptic area – anterior hypothalamus (MPO AH), Nucleus Accumbens (NaC), Olfactory bulb (OB), Olfactory tubercle (OT), Organum vasculosum laminae teriminalis (OVLT), Parabrachial nucleus (PBN), Paraventricular nucleus (PVN), Periaqueductal grey (PAG), Periventricular nucleus hypothalamus (PV), Prefrontal cortex (PFC), Substantia nigra (SN), Suprachiasmatic nucleus (SCN), Supraoptic nucleus (SON), Ventral pallidum (VP), Ventral tegmental area (VTA)
Figure 3
Figure 3
The distribution of V1aR (blue) and OTR (red) binding in male rats. Overall, there is little overlap between the patterns of V1aR and OTR binding. The right column illustrates rat brain images adapted from The Rat Brain Atlas [137]. Dense V1aR binding was found in somatosensory cortex (SSc), piriform cortex (PC), Islands of Calleja (ICj), nucleus accumbens (NAc), lateral septum (LS), lateral posterior bed nucleus of the stria terminalis (BNST) (BNSTlp), nucleus of the lateral olfactory tract (LOT), dentate gyrus (DG), tuberal lateral hypothalamus (TuLH), anteroventral thalamus (AVthal), interstitial nucleus of the posterior limb of the anterior commissure (IPAC), arcuate nucleus of the hypothalamus (ArcN), ventromedial thalamus (VMthal), and medial central amygdala (CeAm). Dense OTR binding was found in the dorsal caudate putamen (CPu), agranular insular cortex (AIP), posterior BNST (BNSTp), medial preoptic area (MOPA), ventromedial hypothalamus (VMH), and later and capsular central amygdala (CeAl/c). Regions where sex differences were identified are underlined. Taken from Dumais and Veenema (2016) with permission.
Figure 4
Figure 4
Diagrammatic representations comparing the primary structures of human OTRs, V1aRs and V1bRs. Amino acid residues conserved between receptors are indicated by dark circles: (A) OTRs and V1aRs, (B) V1aRs and V1bRs, and (C) V1aRs and V1bRs. See [19; 20]
Figure 5
Figure 5
Effects of OT, AVP and highly selective OTR and V1aR agonists and antagonists on a form social communication called flank marking in hamsters. (A) introcerebroventricular injections of both OT and AVP induced flank marking, but AVP is about 100 times more potent than OT (* indicates a significant difference between OT and AVP). (B) Effects of OTR and V1aR agonists on flank marking. The V1aR agonist but not the OTR agonist induced high levels of flank marking (* indicates a signficant difference compared to OT). (C) Effects of OTR and V1aR antagonists on OT-induced flank marking. All three concentrations of the V1aR antagonist completely blocked OT-induced flank marking while the OTR antagonist did not significantly affect flank marking (* indicates a significant difference compared to OT).
Figure 6
Figure 6
Diagrammatic representation of synaptic release with no cross-talk, synaptic release with cross-talk, and non-synaptic release with volume transmission and cross-talk in neurons that produce oxytocin (OT) or arginine-vasopressin (AVP). Synaptic release of OT or AVP is produced by action potentials (AP) that activate an influx of extracellular calcium (Ca2+) through voltage sensitive Ca2+ channels. Non-synaptic release of OT or AVP is produced by the release of Ca2+ from endogenous stores (e.g., endoplasmic reticulum (ER)).
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