The removal of the oxytocin receptor has no effect on monogamy or delivery.
According to recent research from UC San Francisco and Stanford Medicine, the receptor for oxytocin, a hormone thought to be critical for forging social ties, may not perform the critical role that scientists have given to it for the past 30 years. This discovery calls into question a decades-old belief. Prairie voles reproduced without oxytocin receptors and exhibited the same monogamous mating, bonding, and parenting behaviours as other voles. The findings will be published in the journal Neuron on January 27.
Furthermore, although producing less milk than usual female voles, females lacking oxytocin receptors delivered birth and produced milk. The findings suggest that the biology underlying pair bonding and parenting is not solely determined by oxytocin receptors, also known as the “love hormone.”
“While oxytocin has been considered ‘Love Potion #9,’ it seems that potions 1 through 8 might be sufficient,” said psychiatrist Devanand Manoli, MD, PhD, a senior author of the paper and member of the UCSF Weill Institute for Neurosciences. “This study tells us that oxytocin is likely just one part of a much more complex genetic program.”
Prairie voles are studied to better understand the nature of social bonding because they are one of the few mammalian species known to form lifelong monogamous relationships. Using medicines that inhibit oxytocin from attaching to its receptor, researchers discovered that voles were unable to pair bond, giving rise to the theory that the hormone is required for such bonds.
The new experiment arose from Manoli’s similar interests with co-senior author and neurobiologist Nirao Shah, MD, PhD, who was previously at UCSF and is currently at Stanford Medicine. Since teaching about oxytocin studies decades ago, Shah had been interested in the biology of oxytocin and social attachment in prairie voles.
Manoli joined Shah’s group as a postdoctoral investigator in 2007 with the goal of studying the neurology of social bonding. The two used new genetic technology to confirm if oxytocin binding to its receptor was actually the cause causing pair bonding in this 15-year-long study.
They employed CRISPR to create prairie voles deficient in oxytocin receptors. The mutant voles were then examined to see if they could develop long-term partnerships with other voles. The mutant voles formed pair bonds just as easily as normal voles, which surprised the researchers.
“The patterns were indistinguishable,” said Manoli. “The major behavioural traits that were thought to be dependent on oxytocin – sexual partners huddling together and rejecting other potential partners as well as parenting by mothers and fathers – appear to be completely intact in the absence of its receptor.”
Even more remarkable than the pair bonding was the fact that a considerable proportion of the female voles were able to give birth and produce milk for their pups.
Manoli believes that oxytocin plays a more complicated role in both delivery and nursing than previously recognised. Female voles lacking receptors were shown to be completely capable of giving birth in the same period and manner as regular animals, despite the fact that labour was supposed to rely on oxytocin.
The findings shed light on some of the enigmas regarding the hormone’s role in childbirth: Although oxytocin is widely used to induce labour, inhibiting its activity in moms who experience early labour does not work any better than other methods of preventing contractions.
The researchers were caught aback when it came to producing milk and feeding pups. For many decades, oxytocin binding to its receptor was thought to be essential for milk ejection and parental care. However, half of the mutant females were able to nurse and wean their pups successfully, indicating that oxytocin signalling does play a role, but it is less important than previously thought.
“This overturns conventional wisdom about lactation and oxytocin that’s existed for a much longer time than the pair bonding association,” said Shah. “It’s a standard in medical textbooks that the milk letdown reflex is mediated by the hormone, and here we are saying, ‘Wait for a second, there’s more to it than that.'”
Manoli and Shah concentrated on the neurobiology and molecular mechanics of pair bonding since it is thought to hold the key to better treatments for mental illnesses that interfere with a person’s capacity to develop or maintain social ties, such as autism and schizophrenia.
Over the last decade, significant hope has been placed in scientific trials that use oxytocin to treat certain disorders. However, the outcomes were uneven, and none of them revealed a clear path to improvement.
According to the researchers, these findings strongly suggest that the existing hypothesis, in which a single pathway or chemical is responsible for social attachment, is oversimplified. According to them, this result makes sense from an evolutionary standpoint, given the importance of attachment to the survival of many social species.
“These behaviours are too important to survival to hinge on this single point of potential failure,” said Manoli. “There are likely other pathways or another genetic wiring to allow for that behaviour. Oxytocin receptor signalling could be one part of that program, but it’s not the be-all-end-all.”
The discovery guides the researchers in new directions for improving the lives of those who are having difficulty making social bonds. “If we can find the key pathway that mediates attachment and bonding behaviour,” Shah said, “We’ll have an eminently druggable target for alleviating symptoms in autism, schizophrenia, and many other psychiatric disorders.”