There's more to love than a single hormone.

That's the conclusion of a study of prairie voles that were genetically altered to ignore signals from the "love hormone" oxytocin.

The study, published in the journal Neuron, comes after decades of research suggesting that behaviors like pair-bonding and parenting depend on oxytocin. Many of those studies involved prairie voles, which mate for life and are frequently used to study human behavior.

"Oxytocin might be 'love potion number nine,' but one through eight are still in play," says Dr. Devanand Manoli, an author of the paper and a psychiatrist at the University of California, San Francisco.

The finding is important, but not surprising, says Sue Carter, a professor of psychology at the University of Virginia and distinguished university scientist at Indiana University, Bloomington, who was not involved in the study.

"The process of forming a secure social bond lasting for a very long period of time is too important to restrict to a single molecule," says Carter, who helped discover the link between oxytocin and social behavior in prairie voles more than 30 years ago.

Carter believes oxytocin is the central player in behaviors including pair bonding, parenting and lactation. But she says animals that are born without the ability to respond to the hormone appear to find other ways to replicate behaviors that are critical to their survival.

A big surprise

The finding that pair bonding occurs without oxytocin came as a surprise to the team who did the experiment.

"We were shocked because that was really, really not what we expected, says Manoli, who worked with a team that included Dr. Nirao Shah at Stanford University, and Dr. Kristen Berendzen of UCSF.

The team's experiment was designed to disrupt pair-bonding and other oxytocin-related behaviors in prairie voles.These include parenting, milk production, forming social attachments, and socially monogamous pair bonding.

"One of the behaviors that's really the most adorable is this huddling behavior," Manoli says. "They'll sometimes groom. Sometimes they'll just fall asleep because it's very calming. And that's very specific to the pair-bonded partner."

Previous studies had found that these behaviors vanish when scientists use drugs to block oxytocin in adult prairie voles. So the team expected they would get a similar result using a gene editing technique to eliminate the oxytocin receptor, a molecule that allows cells to respond to the hormone.

This time the team removed fertilized eggs from female prairie voles, edited the genes, and then placed the embryos in females that were hormonally ready for pregnancy.

The result was pups that appeared normal. And when these pups grew up, they formed pair bonds just like other prairie voles.

The females were even able to produce milk for their offspring, though the amount was less than with unaltered animals.

"My initial response was, okay we have to do this three more times because we need to make sure this is 100% real," Manoli says. But repeated experiments confirmed the finding.

More than one "love hormone"?

It's still a mystery what drives pair-bonding in the absence of oxytocin. But it's clear, Manoli says, that "because of evolution, the parts of the brain and the circuitry that are responsible for pair-bond-formation don't rely [only] on oxytocin."

In retrospect, he says, the result makes sense because pair bonding is essential to a prairie vole's survival. And evolution tends to favor redundant systems for critical behaviors.

The finding could help explain why giving oxytocin to children with autism spectrum disorder doesn't necessarily improve their social functioning, Manoli says.

"There's not a single pathway," he says. "But rather, these complex behaviors have really complicated genetics and complicated neural mechanisms."

One possible explanation for the result is that when prairie voles lack an oxytocin system almost from conception, they are able to draw on other systems to develop normally, Carter says.

That could mean using a different molecule, vasopressin, Carter says, which also plays a role in social bonding in both humans and prairie voles. And there may be more molecules that have yet to be discovered.

A full understanding of the biology underlying social bonds is critical to understanding human behavior, Carter says. It also could explain why humans generally don't thrive without positive relationships, especially during childhood.

"We can live without fine clothing. We can live without too much physical protection. But we cannot live without love," Carter says.

Which may be the reason we might be able to love without oxytocin.

Copyright 2023 NPR. To see more, visit https://www.npr.org.

Transcript

ARI SHAPIRO, HOST:

It's known as the love hormone, but a new study suggests that label is misleading. NPR's Jon Hamilton reports on what scientists are learning about oxytocin.

JON HAMILTON, BYLINE: When romance is in the air, a couple's oxytocin levels rise. That's true for both people and prairie voles, mouse-like rodents that mate for life and are often used to study human behavior. Dr. Dev Manoli, a psychiatrist at the University of California San Francisco, says prairie vole couples share a nest and even co-parent.

DEV MANOLI: One of the behaviors that's really, you know, sort of the most adorable is this huddling behavior, just sort of huddling with each other. They'll sometimes groom. Sometimes they just fall asleep because it's very calming. And that's very specific to the pair-bonded partner.

HAMILTON: Decades of research has suggested that oxytocin is critical to that sort of behavior. So Manoli and a team of scientists did an experiment designed to disrupt pair bonding. They removed fertilized eggs from female prairie voles and edited the genes to neutralize the effects of oxytocin. After that, Manoli says, they let the cells grow.

MANOLI: So we culture them for a few days and then put them into what's called a pseudo pregnant female.

HAMILTON: An animal that's hormonally ready to carry an embryo. The result was pups that appeared normal. And when these pups grew up, they formed pair bonds just like other prairie voles. Manoli says females were even able to produce milk for their offspring, a process usually mediated by oxytocin.

MANOLI: We were shocked because that was really, really not what we expected. And, you know, my initial response was, OK, we have to do this three more times because we need to be sure that this is 100% real. But also, what's going on?

HAMILTON: Repeated experiments confirmed the finding, which appears in the journal Neuron. Manoli says it's still a mystery how pair bonding occurs in the absence of oxytocin. But he says the study makes one thing clear.

MANOLI: Because of evolution, the parts of the brain and the circuitry that are responsible for pair bond formation don't really rely on oxytocin. They don't need it.

HAMILTON: In other words, Manoli says...

MANOLI: Oxytocin might be love potion No. 9, but one through eight are still in play. Right? There's more there than that one entry point.

HAMILTON: Manoli says in retrospect, the result makes sense because pair bonding is essential to a prairie vole's survival, and evolution tends to favor redundant systems for critical behaviors. He says the result also may help explain why giving oxytocin to children with autism spectrum disorder doesn't reliably improve their social functioning.

MANOLI: There's not a single pathway, but rather, these complex behaviors have really complicated genetics and complicated neural mechanisms.

HAMILTON: Many scientists who study oxytocin say they're uncomfortable with the term love hormone. Sue Carter of the University of Virginia and Indiana University helped discover the link between oxytocin and monogamy in prairie voles. But she says she never assumed the hormone was acting alone.

SUE CARTER: The process of forming a secure social bond lasting for a very long period of time is too important to restrict to a single molecule.

HAMILTON: Carter says a different molecule called vasopressin also contributes to social bonding, and there may be others, she says, though she believes oxytocin is the major player.

CARTER: We can live without fine clothing. We can even live without too much physical protection. But we cannot live without love.

HAMILTON: Which may be the reason we can love without oxytocin. Jon Hamilton, NPR News.

(SOUNDBITE OF SONG, "OXYTOCIN")

BILLIE EILISH: (Singing) Can't take it back once it's been set in motion. You know I need you for the oxytocin. If you find it hard to swallow, I can loosen up your collar 'cause as long as you're still breathing, don't you even think of leaving. Transcript provided by NPR, Copyright NPR.

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