Oxytocin and vasopressin: Signalling, behavioural modulation and potential therapeutic effects

Abstract

Oxytocin (OT) and vasopressin (AVP) are endogenous ligands for OT and AVP receptors in the brain and in the peripheral system. Several studies demonstrate that OT and AVP have opposite roles in modulating stress, anxiety and social behaviours. Interestingly, both peptides and their receptors exhibit high sequence homology which could account for the biased signalling interaction of the peptides with OT and AVP receptors. However, how and under which conditions this crosstalk occurs in vivo remains unclear. In this review we shed light on the complexity of the roles of OT and AVP, by focusing on their signalling and behavioural differences and exploring the crosstalk between the receptor systems. Moreover, we discuss the potential of OT and AVP receptors as therapeutic targets to treat human disorders, such as autism, schizophrenia and drug abuse. LINKED ARTICLES: This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.8/issuetoc.

Keywords: GPCR; anxiety; crosstalk; oxytocin; social behaviour; substance use disorder; vasopressin.

FIGURE 1

Amino acid sequences of human oxytocin and vasopressin neuropeptides (a) and their receptors (b). (a) Primary sequence of oxytocin and vasopressin in single letter amino acid code. (b) Primary sequence of human OT receptors (OTR), and V_1A (AVPR1a), V_1B (AVPR1b) and V₂ (AVPR2) receptors. The amino acid residues that have been described to interact with the endogenous ligands vasopressin (AVP) and oxytocin (OT), as well as the co-factors Mg²⁺ and cholesterol (Ct) are highlighted by the dashed rectangles. Amino acids in bold represent residues that are conserved in the OT, V_1A, V_1B and V₂ receptors. * marks residues that are conserved among all the receptors. # marks residues that are conserved among OT, V_1A and V_1B receptors.: marks residues that have same functional groups. Blue represents amino acids with negative charged side chain; magenta represents residues with positive charge; green represents residues with polar uncharged side chain; purple represents residues with hydrophobic side chain. OTR, oxytocin receptor; V_1A, V_1B and V₂, subtypes of vasopressin receptors; TM, transmembrane; EL, extracellular loop; IL, intracellular loop. Sequence obtained from uniport.org

FIGURE 2

Schematic representation of context-dependent modulations of oxytocin and vasopressin. Oxytocin can act on different brain regions depending on the social context, leading to different behavioural outcomes. Expression of V_1A receptors (AVPR1a) is modulated by housing or sexual experience, which increases or decreases aggression. CeA, central amygdala; Hyp, hypothalamus; LS, lateral septum; OT, oxytocin; AVP, vasopressin. Figure was generated using information obtained from Albers, 2012; Johnson & Young, 2015; Guzmán et al., 2013

FIGURE 3

Behaviours modulated by oxytocin and vasopressin and their potential pharmacotherapeutic applications in autism, schizophrenia and SUD. Intranasal manipulation of oxytocinergic and vasopressinergic systems lead to improvement in symptoms observed in these disorders. Symbols indicate (+) increase or (−) decrease in the respective behaviour. SUD, substance use disorder