Oxytocin, vasopressin and pair bonding: implications for autism

Abstract

Understanding the neurobiological substrates regulating normal social behaviours may provide valuable insights in human behaviour, including developmental disorders such as autism that are characterized by pervasive deficits in social behaviour. Here, we review the literature which suggests that the neuropeptides oxytocin and vasopressin play critical roles in modulating social behaviours, with a focus on their role in the regulation of social bonding in monogamous rodents. Oxytocin and vasopressin contribute to a wide variety of social behaviours, including social recognition, communication, parental care, territorial aggression and social bonding. The effects of these two neuropeptides are species-specific and depend on species-specific receptor distributions in the brain. Comparative studies in voles with divergent social structures have revealed some of the neural and genetic mechanisms of social-bonding behaviour. Prairie voles are socially monogamous; males and females form long-term pair bonds, establish a nest site and rear their offspring together. In contrast, montane and meadow voles do not form a bond with a mate and only the females take part in rearing the young. Species differences in the density of receptors for oxytocin and vasopressin in ventral forebrain reward circuitry differentially reinforce social-bonding behaviour in the two species. High levels of oxytocin receptor (OTR) in the nucleus accumbens and high levels of vasopressin 1a receptor (V1aR) in the ventral pallidum contribute to monogamous social structure in the prairie vole. While little is known about the genetic factors contributing to species-differences in OTR distribution, the species-specific distribution pattern of the V1aR is determined in part by a species-specific repetitive element, or 'microsatellite', in the 5' regulatory region of the gene encoding V1aR (avpr1a). This microsatellite is highly expanded in the prairie vole (as well as the monogamous pine vole) compared to a very short version in the promiscuous montane and meadow voles. These species differences in microsatellite sequence are sufficient to change gene expression in cell culture. Within the prairie vole species, intraspecific variation in the microsatellite also modulates gene expression in vitro as well as receptor distribution patterns in vivo and influences the probability of social approach and bonding behaviour. Similar genetic variation in the human AVPR1A may contribute to variations in human social behaviour, including extremes outside the normal range of behaviour and those found in autism spectrum disorders. In sum, comparative studies in pair-bonding rodents have revealed neural and genetic mechanisms contributing to social-bonding behaviour. These studies have generated testable hypotheses regarding the motivational systems and underlying molecular neurobiology involved in social engagement and social bond formation that may have important implications for the core social deficits characterizing autism spectrum disorders.

Figure 1

Autoradiograms illustrating the distribution of oxytocin receptors (a,b) and vasopressin receptors (c,d) in the monogamous prairie vole (a,c) and non-monogamous meadow vole (b,d). Note the species differences in oxytocin receptors in the NAcc and the vasopressin receptors in the VP. PFC, prefrontal cortex; CP, caudate putamen; NAcc, nucleus accumbens; LS, lateral septum; VP, ventral pallidum.

Figure 2

(a) Schematic of the structure of the vasopressin receptor gene avpr1a in voles and AVPR1A in primates. The black bars represent the transcribed region of the gene. The hatched bars represent the microsatellite sequences in the 5′ flanking region of the gene as discussed in the text. Numbers above the microsatellites indicate the relative position upstream of the transcription start site. (b) Autoradiograms illustrating the differences in vasopressin receptor binding in prairie voles with either short (top row) or long (bottom row) versions of the microsatellite in the avpr1a gene. Note the strain differences in the olfactory bulb (OB), lateral septum (LS) and the hypothalamus (HYP).