Turning a decades-old dogma on its head, recent research from scientists at UC San Francisco and Stanford Medicine shows that the receptor for oxytocin, a hormone considered essential to forming social bonds, may not play the critical role that scientists have assigned to it for the past 30 years.

Within the study, appearing Jan. 27, 2023 in Neuron, the team found that prairie voles bred without receptors for oxytocin and showed the identical monogamous mating, attachment, and parenting behaviors as regular voles. As well as, females without oxytocin receptors gave birth and produced milk, though in smaller quantities, than atypical female voles.

The outcomes indicate that the biology underlying pair bonding and parenting is not purely dictated by the receptors for oxytocin, sometimes known as the “love hormone.”

While oxytocin has been considered ‘Love Potion #9,’ it appears that evidently potions 1 through 8 is likely to be sufficient. This study tells us that oxytocin is probably going only one a part of a way more complex genetic program.”

Devanand Manoli, MD, PhD, psychiatrist, senior writer of the paper and member of the UCSF Weill Institute for Neurosciences

CRISPR voles pack a surprise

Because prairie voles are one in all the few mammalian species known to form lifelong monogamous relationships, researchers study them to higher understand the biology of social bonding.

Studies within the Nineteen Nineties using drugs that prevent oxytocin from binding to its receptor found that voles were unable to pair bond, giving rise to the concept the hormone is crucial to forming such attachments.

The present project emerged from shared interests between Manoli and co-senior writer and neurobiologist Nirao Shah, MD, PhD, then at UCSF and now at Stanford Medicine. Shah had been involved in the biology of oxytocin and social attachment in prairie voles since teaching in regards to the oxytocin studies many years earlier. Manoli, who wanted to analyze the neurobiology of social bonding, joined Shah’s lab in 2007 as a postdoctoral scholar.

For this study, 15 years within the making, the 2 applied recent genetic technologies to substantiate if oxytocin binding to its receptor was indeed the factor behind pair bonding. They used CRISPR to generate prairie voles that lack functional oxytocin receptors. Then, they tested the mutant voles to see whether or not they could form enduring partnerships with other voles.

To the researchers’ surprise, the mutant voles formed pair bonds just as readily as normal voles.

“The patterns were indistinguishable,” said Manoli. “The most important behavioral traits that were regarded as depending on oxytocin – sexual partners huddling together and rejecting other potential partners in addition to parenting by moms and dads – seem like completely intact within the absence of its receptor.”

Labor and lactation

Much more surprising for Manoli and Shah than the pair bonding was the incontrovertible fact that a major percentage of the feminine voles were able to provide birth and supply milk for his or her pups.

Oxytocin is more likely to have a task in each birth and lactation, but one which is more nuanced than previously thought, Manoli said. Female voles without receptors proved perfectly able to giving birth, on the identical timeframe and in the identical way because the regular animals, despite the fact that labor has been thought to depend on oxytocin.

The outcomes help to clear up among the mystery surrounding the hormone’s role in childbirth: Oxytocin is often used to induce labor but blocking its activity in moms who experience premature labor is not higher than other approaches for halting contractions.

When it got here to producing milk and feeding pups, nevertheless, the researchers were greatly surprised. Oxytocin binding to its receptor has been considered essential for milk ejection and parental take care of many many years, but half of the mutant females were capable of nurse and wean their pups successfully, indicating that oxytocin signaling plays a task, nevertheless it is less vital than previously thought.

“This overturns conventional wisdom about lactation and oxytocin that is existed for a for much longer time than the pair bonding association,” said Shah. “It’s a regular in medical textbooks that the milk letdown reflex is mediated by the hormone, and here we’re saying, ‘Wait a second, there’s more to it than that.'”

Hope for social connection

Manoli and Shah focused on understanding the neurobiology and molecular mechanisms of pair bonding since it is assumed to carry the important thing to unlocking higher treatments for psychiatric conditions, reminiscent of autism and schizophrenia, that interfere with an individual’s ability to form or maintain social bonds.

Over the past decade, much hope was pinned on clinical trials using oxytocin to handle those conditions. But those results were mixed, and none has illuminated a transparent path to improvement.

The researchers said their study strongly suggests that the present model – a single pathway or molecule being accountable for social attachment –is oversimplified. This conclusion is sensible from an evolutionary perspective, they said, given the importance of attachment to the perpetuation of many social species.

“These behaviors are too vital to survival to hinge on this single point of potential failure,” said Manoli. “There are likely other pathways or other genetic wiring to permit for that behavior. Oxytocin receptor signaling could possibly be one a part of that program, nevertheless it’s not the be-all end-all.”

The invention points the researchers down recent paths to improving the lives of individuals struggling to search out social connection.

“If we will find the important thing pathway that mediates attachment and bonding behavior,” Shah said, “We’ll have an eminently druggable goal for alleviating symptoms in autism, schizophrenia, many other psychiatric disorders.”

Source:

University of California – San Francisco

Journal reference:

Berendzen, K.M., et al. (2023) Oxytocin receptor shouldn’t be required for social attachment in prairie voles. Neuron. doi.org/10.1016/j.neuron.2022.12.011.