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Fresh Questions About Oxytocin as the ‘Love Hormone’ Behind Pair Bonding

Fresh Questions About Oxytocin as the ‘Love Hormone’ Behind Pair Bonding

 


Three scientists wearing lab coats and face masks prepare a maze for a study on voles.
Devanand Manoli, MD, PhD studies the effects of oxytocin, the molecule behind pair bonding. He works with his postdoctoral fellows in psychiatry, Dr. Ruchira Sharma (left) and Kristen Berendzen, MD, to assemble partitions in the maze to videotape voles in the lab. Photo by Barbara Reese

A new study by scientists at the University of California, San Francisco and the Stanford University School of Medicine has flipped a decades-old dogma, suggesting that the receptor for oxytocin, a hormone thought to be essential for forming social bonds, could It indicates that you may not fulfill the important role assigned to you. For the last 30 years.

In this study, on January 27, 2023 neuronThe research team found that prairie voles reared without oxytocin receptors exhibited the same monogamous mating, attachment and parenting behaviors as normal voles. Furthermore, females without oxytocin receptors gave birth and produced milk, albeit in smaller quantities than normal female voles.

The results indicate that the biology underlying mating bonding and parenting is not determined purely by receptors for oxytocin, sometimes referred to as the “love hormone.”

“Oxytocin has been considered ‘love potion number nine,’ but potions one through eight may suffice,” said the psychiatrist. devanand manoliMD, PhD, senior author and member of the paper UCSF Weill Neuroscience Institute“This study indicates that oxytocin is likely just part of a much more complex genetic program.”

Oxytocin plays a minor role in voles

A graphic representation of a hexagon with protruding lines showing the structure of a protein or receptor.  One structure is magenta and the other is white.both remain on the pink background

Prairie voles are one of the few mammalian species known to form lifelong monogamous relationships, helping us understand the biology of social bonds.

Researchers found that even voles that lack oxytocin receptors can form monogamous bonds with mates, give birth within normal timeframes, and produce lactate.

These findings may indicate a significantly smaller role for oxytocin in social bonding.

CRISPR voles pack a surprise

Prairie voles are one of the few mammalian species known to form lifelong monogamous relationships, so researchers are interested in using them to better understand the biology of social bonding. Researching.

Studies in the 1990s using drugs that prevented oxytocin from binding to its receptors found that voles were unable to mate, giving rise to the idea that hormones were essential to the formation of such attachments. rice field.

The current project grew out of a shared interest between Manoli and co-lead author and neurobiologist Nirao Shah, MD, PhD, then UCSF, now Stanford Medicine. Ever since Shah taught about oxytocin research decades ago on Prairie, he has been interested in the biology of oxytocin and social attachment in voles. Wanting to investigate the neurobiology of social cohesion, Manoli joined Shah’s lab in 2007 as a postdoctoral fellow.

In this study, the two applied a new genetic technique to see if the binding of oxytocin to its receptor was indeed the factor behind pair binding. They used his CRISPR to generate Prairie his voles that lack functional oxytocin receptors. Mutated voles were then tested to see if they could form lasting partnerships with other voles.

To the researchers’ surprise, the mutant voles formed pairs just as easily as normal voles.

“The pattern was indistinguishable,” said Manoli. “The key behavioral traits thought to be dependent on oxytocin — sexual partner snuggling, rejection of other potential partners, and maternal and paternal parenting — can be observed even in the absence of its receptors. It appears to be completely intact.”

labor and breastfeeding

Even more surprising to Manori and Shah than their mating bond was the fact that a good percentage of female voles were able to give birth and feed their puppies.

Oxytocin likely plays a role in both labor and lactation, but it plays a more nuanced role than previously thought, said Manoli. Despite this, female voles, which have no receptors, proved to be perfectly capable of giving birth in the same timeframe and in the same manner as normal animals.

The results help shed light on some of the mysteries surrounding the role of hormones in childbirth. Blocking is superior to other approaches to stopping labor.

But when it came to milk production and feeding the puppies, the researchers were taken aback. The binding of oxytocin to its receptors has been considered essential for milk ejection and parental care for decades.

“This overturns conventional wisdom about lactation and oxytocin that has existed for much longer than pair bonding associations,” says Shah. It’s standard in medical textbooks, and here we say, ‘Wait a minute, there’s more than that.'”

Hope for social connection

Manoli and Shah focused on understanding the neurobiology and molecular mechanisms of pair bonding. This is because it is believed to hold the key to unlocking better treatments for psychiatric conditions such as autism and schizophrenia that interfere with a person’s ability to form or maintain social bonds.

Over the past decade, there has been much hope for clinical trials using oxytocin to address these symptoms. However, these results were mixed and none provided a clear path to improvement.

The researchers said their work strongly suggests that the current model of a single pathway or molecule responsible for social attachment is an oversimplification. Given the importance of attachment to species perpetuation, the conclusion makes sense from an evolutionary perspective, they said.

“These behaviors are so critical to survival that we cannot rely on this single point of potential failure,” Manoli said. It is possible that there is a systematic wiring: oxytocin receptor signaling may be part of that program, but it is not the whole.”

The findings point researchers to a new avenue for improving the lives of people who struggle to find social connections.

“If we can find the key pathways that mediate attachment and bonding behavior, we have a highly druggable target for alleviating the symptoms of autism, schizophrenia, and many other psychiatric disorders. you can put it in.”

author: Additional authors are: Ruchira SharmaRose Larios, Nastacia Goodwin, Michael Sherman, and Isidero Espineda of UCSF; Maricruz Alvarado Mandujano, YiChao Wei, Srinivas Parthasarthy, and Joseph Knoedler of Stanford University; Forrest Rogers, Trenton Simmons, Adele Seelke, Jessica Bond, and Karen Bales of UC Davis; Annaliese Biery of Berkeley.

Funding: This work was supported by NIH grants R01MH123513, R01MH108319, DP1MH099900 and R25MH060482, NSF grant 1556974, and philanthropy. See research for more information.

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