UC Berkeley study finds key role for oxytocin in friendship formation

James B. Milliken
James B. Milliken
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A study from the University of California, Berkeley suggests that oxytocin, often called the “love hormone,” plays a significant role in forming friendships. Oxytocin is known to be released during activities such as sex, childbirth, breastfeeding, and various social interactions. It is associated with feelings of attachment and trust but also has links to aggression.

Recent research using prairie voles—a rodent species known for forming stable relationships—has challenged the idea that oxytocin is necessary for long-term mate bonding or parenting behaviors. However, UC Berkeley researchers focused on how oxytocin affects peer relationships among these animals.

“Prairie voles are special because they allow us to get at the neurobiology of friendship and how it’s similar to and different from other types of relationships,” said Annaliese Beery, a UC Berkeley associate professor of integrative biology and neuroscience and senior author of the study.

Beery and Alexis Black, an integrative biology graduate student at UC Berkeley and co-first author, observed that prairie voles lacking oxytocin receptors took longer than typical voles to form peer bonds. In normal conditions, close vole friends huddle together or groom each other.

“Oxytocin seems to be particularly important in the early formation phase of relationships and especially in the selectivity of those relationships: ‘I prefer you to this stranger,’ for example,” Beery said. “The animals that didn’t have intact oxytocin signaling took longer to form relationships. And then when we challenged those relationships by making new groups, they lost track of their original partners right away.”

These genetically modified voles were created in collaboration with Dr. Devanand Manoli’s laboratory at UC San Francisco. The altered animals showed less effort in staying close to friends and were less avoidant or aggressive toward strangers compared with normal voles.

“In other words, oxytocin is playing a crucial role not so much in how social they are, but more in who they are social with, their selectivity,” she said.

The team used a novel nanosensor developed by postdoctoral fellow Natsumi Komatsu and Markita Landry—a UC Berkeley professor—to track changes in oxytocin release within the brain. They found that lacking oxytocin receptors led to lower levels of release from fewer sites in key brain regions involved in social reward.

“That helped us understand the feedback consequences of lacking this receptor, and how oxytocin signaling was altered in the brain,” said Beery.

The findings were published August 8 in Current Biology.

Beery’s broader research includes field studies on various rodent species’ social behavior across North America and South America. She aims to determine if selective peer bonds predate monogamous mating systems among rodents.

“While most rodents prefer to interact with unfamiliar individuals, it turns out that the majority of vole species we’ve tested in our early trials form peer-partner preferences, which is what we call these selective friendships. So there seems to be this widespread tendency to bond,” Beery said. “But only a couple of those species are also monogamous. Someday, I hope to be able to tell you, ‘Do selective peer relationships precede the development of monogamy? Is that why monogamy has evolved so many times in this genus?’ I think this familiarity preference is deeply rooted.”

A previous 2023 study involving some of these same genetically engineered prairie voles suggested that even without responding to oxytocin signals, these animals maintained typical mating attachments and parenting behaviors; however, subsequent research indicated it took them about twice as long as normal voles to establish such bonds.

Further experiments by Beery’s group showed that while regular prairie voles formed partner preferences within about 24 hours when housed together—demonstrating loyalty by choosing their partner over strangers—the receptor-deficient animals required up to a week before displaying similar preferences.

“Wild-type animals form this incredibly robust preference within one day of co-housing, but the null mutants have no sign of a relationship after 24 hours. After a week, they mostly get there, and the lifetime partners look no different from each other,” Beery said. “Our conclusion from that experiment is that oxytocin isn’t required to have a relationship, but it’s really important in those early phases of a relationship to facilitate it happening quickly and efficiently.”

In mixed-group settings simulating party environments for voles—where multiple rooms allowed free movement—normal animals stayed near familiar companions initially before mingling more widely; mutant voles did not show any preference for familiar peers under these conditions.

“They can all separate, they can all come together, or they can hang out in any combinations that they want,” she said. “The wild-type animals keep track of who they know. It’s like if I went to a party with a friend… The voles that lack oxytocin receptors just mixed. It was as if they didn’t even have a partner in there with them.”

Tests measuring how hard female prairie voles worked (by pressing levers) for access revealed wild-type females preferred established mates or friends over strangers; mutant females pressed more for mates but not for peers.

“Female wild-type voles typically press more to get their partner than to get a stranger… The oxytocin receptor deficient mutants also press more…for their mating partner but not for peer relationships,” Beery explained.”That makes sense at some level because we think mate relationships are more rewarding than peer relationships…”

The lack of functional oxytocin receptors thus delayed bond formation between peers while reducing long-term selectivity among friends; affected animals were also less aggressive toward unknown individuals.

“You can see contributions of oxytocin signaling…to both sides of selectivity,” Beery noted.”On the prosocial side,…it’s involved in wanting…a known friend…, while on the antisocial side,…it’s aiding…in rejecting an unfamiliar animal…”

Markita Landry’s lab developed carbon nanotube-based nanosensors coated with DNA sequences specific for binding oxytoxin molecules—which then emit infrared light—to help visualize real-time release events inside living brains at synapses (cellular junctions). No excess levels were detected; instead overall release decreased where expected due partly perhaps compensatory mechanisms via related neuropeptide systems may exist elsewhere across species lines.

Co-authors included Jiaxuan Zhao (UC Berkeley), Scarlet Taskey (UC Berkeley), Nicole Serrano (UC Berkeley), Ruchira Sharma (UCSF), Natsumi Komatsu (now assistant professor at University Illinois), alongside support provided through National Science Foundation CAREER award 2239635 & NIH grant R01MH132908.



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