Mu-opioid receptor (OPRM1) variation, oxytocin levels and maternal attachment in free-ranging rhesus macaques Macaca mulatta.

Abstract

Understanding the genetic and neuroendocrine basis of the mother-infant bond is critical to understanding mammalian affiliation and attachment. Functionally similar non-synonymous mu-opioid receptor (OPRM1) SNPs have arisen and been maintained in humans (A118G) and rhesus macaques (C77G). In rhesus macaques, variation in OPRM1 predicts individual differences in infant affiliation for mothers. Specifically, infants carrying the G allele show increased distress on separation from their mothers, and spend more time with them upon reunion, than individuals homozygous for the C allele. In humans, individuals possessing the G allele report higher perceptions of emotional pain on receiving rejection by social partners. We studied maternal behavior over the course of a year among free-ranging female rhesus macaques on Cayo Santiago, Puerto Rico. We then trapped females and collected blood samples, from which we assessed OPRM1 genotype; we also collected CSF samples from which we measured oxytocin (OT) levels. We show that females possessing the G allele restrain their infants more (i.e. prevent infants from separating from them by pulling them back) than females homozygous for the C allele. Females possessing the G allele also show higher OT levels when lactating, and lower OT levels when neither lactating nor pregnant, than females homozygous for the C allele. This is the first study to demonstrate an association between OPRM1 genotype and maternal attachment for infants, and is one of the first studies of any free-ranging primate population to link functional genetic variation to behavior via potentially related neuroendocrine mechanisms.

Social Pain and the Brain: Controversies, Questions, and Where to Go from Here

“…Moreover, in rhesus monkeys, variation in the mu-opioid receptor gene (OPRM1) relates to attachment behaviors in both offspring and mothers. Infants who carry the G allele, which is known to relate to greater physical pain sensitivity (Chou 2006, Sia et al 2008, show increased distress upon separation from their mothers (Barr et al 2008), and mothers who carry the G allele are more likely to prevent their infants from separating from them (Higham et al 2011) (possibly because of the increased distress associated with separation). Together, these studies show that opioids may be an important shared substrate underlying physical and social pain.…”

Genetic mechanisms of parenting

“…Additional closely related systems might also be involved. For instance, variation in the mu opioid receptor gene, OPRM1, is associated with maternal attachment to infants in freeranging rhesus macaques (Higham et al, 2011). Mu opioid receptor genes are good candidate genes for study in human parenting for several reasons: they are implicated in social reward processing in the NA of the rat (Trezza et al, 2011) and are regulated by both the dopamine and oxytocin systems in the brain (Gigliucci et al, 2014).…”

Oxytocin under opioid antagonism leads to supralinear enhancement of social attention

“…Specifically, μ-opioid receptors have been studied in relation to reward, emotion, and behavior in the social domain (12) and are strongly expressed in reward-related regions of the primate brain (13). In rhesus macaques, carrying the G allele of the μ-opioid receptor gene OPRM1, compared with homozygous C alleles, is associated with stronger maternal attachment in infants (14) and more effective prevention of infant separation in mothers (15). Additionally, opioid agonists, such as morphine, decrease physical contact between social partners, whereas NAL administration increases solicitation for social contact, such as grooming and proximity (16)(17)(18)(19).…”