
Prairie voles mate for life and are frequently used to study human behavior.
Todd H. Ahern/Emory University
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Todd H. Ahern/Emory University

Prairie voles mate for life and are frequently used to study human behavior.
Todd H. Ahern/Emory University
There’s more to love than just one hormone.
That’s the finding of a study of prairie voles that were genetically engineered to ignore signals from oxytocin, the «love hormone.»
The study, published in the journal neuron, comes after decades of research suggesting that behaviors such as pairing and parenthood are dependent on oxytocin. Many of these studies involved prairie voles, which mate for life and are frequently used to study human behavior.
«Oxytocin might be ‘love potion number nine,’ but love potion number 9 is still in play,» says Dr. Devanand Manoli, author of the paper and a psychiatrist at the University of California at San Francisco.

The finding is important, but not surprising, says Sue Carter, professor of psychology at the University of Virginia and distinguished academic scientist at Indiana University, Bloomington, who was not involved in the study.
«The process of forming a secure social bond over a very long period of time is too important to be limited to a single molecule,» says Carter, who helped discover the link between oxytocin and social behavior in voles from the grasslands over 30 years ago.
Carter believes that oxytocin is the central player in behaviors including pair bonding, parenthood, and lactation. But she says animals born without the ability to respond to the hormone seem to find other ways to replicate behaviors essential to their survival.
A big surprise
The finding that pairwise binding occurs without oxytocin came as a surprise to the team doing the experiment.
«We were shocked because it was really, really not what we expected,» said Manoli, who worked with a team including Dr. Nirao Shah of Stanford University and Dr. Kristen Berendzen of the UCSF.
The team’s experiment was designed to disrupt pair bonding and other oxytocin-related behaviors in prairie voles, including parenting, milk production, social attachment formation and bonding. of socially monogamous couples.

Prairie voles don’t need oxytocin receptors to form pairs, a new study has found.
Nastasia Goodwin
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Nastasia Goodwin

Prairie voles don’t need oxytocin receptors to form pairs, a new study has found.
Nastasia Goodwin
«One of the behaviors that’s really the most adorable is that cuddling behavior,» Manoli says. «They sometimes groom. Sometimes they just fall asleep because it’s very soothing. And it’s very specific to the pair bonded partner.»
Previous studies had shown that these behaviors disappear when scientists use drugs to block oxytocin in adult prairie voles. The team therefore expected to obtain a similar result by using a gene editing technique to eliminate the receptor for oxytocin, a molecule that allows cells to respond to the hormone.
This time, the team took fertilized eggs from female prairie voles, edited the genes, and then placed the embryos into females that were hormonally ready for pregnancy.
The result was puppies that looked normal. And when these pups grew up, they paired up like other prairie voles.
The females were even able to produce milk for their offspring, although the amount was less than that of the unmodified animals.
«My initial response was, okay, we have to do it three more times because we have to make sure it’s 100% real,» Manoli says. But repeated experiments confirmed the finding.
More of a «love hormone»?
It’s still a mystery what drives pair bonding in the absence of oxytocin. But it’s clear, says Manoli, that «because of evolution, the parts of the brain and the circuits that are responsible for forming pairwise bonds do not depend [only] on oxytocin.»
In retrospect, he says, the result makes sense, because pairwise bonding is critical to a prairie vole’s survival. And evolution tends to favor redundant systems for critical behaviors.
The finding could help explain why giving children with autism spectrum disorders oxytocin doesn’t necessarily improve their social functioning, Manoli says.

“There is no one way,” he says. «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 tap into 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 humans and prairie voles. And there may be other molecules that have not yet been discovered.
A full understanding of the biology underlying social connections is key to understanding human behavior, Carter says. It could also explain why humans generally don’t thrive without positive relationships, especially during childhood.
«We can live without nice clothes. We can live without too much physical protection. But we can’t live without love,» Carter says.
Maybe that’s why we could love without oxytocin.