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.

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