New questions about oxytocin as the ‘love hormone’ behind pair bonding

summary: The “love hormone” oxytocin may not play a crucial role in bonding as previously thought. Removal of oxytocin receptors in animal models still results in monogamous mating, attachment, and parental bonding behaviors, although females without the receptor produce less milk. The results show that parenting is not dictated by oxytocin receptors.

Source: University of California, San Francisco

Turning a decades-old dogma on its head, new research by scientists at the University of California, San Francisco and Stanford Medicine shows that the receptor for oxytocin, a hormone considered essential for the formation of social bonds, may not play the critical role that scientists assigned it to for the past 30 years. .

In the study, which appeared January 27, 2023 in the nervousThe team found that prairie mice bred without oxytocin receptors showed the same monogamous, attachment, and parenting behaviors as normal mice. In addition, females that do not have oxytocin receptors give birth and produce milk, albeit in smaller quantities, than normal female mice.

The findings suggest that the biology behind couple bonding and parenting is not entirely dictated by oxytocin receptors, which are sometimes referred to as the “love hormone.”

“While oxytocin was considered the ‘number 9 love dose,’ it appears that doses 1 through 8 may be sufficient,” said psychiatrist Devanand Manoli, MD, PhD, senior author on the paper and a member of the UCSF Weill Institute for Neuroscience. “This study tells us that oxytocin is likely just one part of a more complex genetic programme.”

CRISPR Voles Surprise Pack

Because voles are one of the few mammalian species known to form lifelong monogamous relationships, researchers are studying them to better understand the biology of social bonding.

Studies done in the 1990s using drugs that prevent oxytocin from binding to its receptors found that rats were unable to make a pair bond, leading to the idea that the hormone is needed to form such bonds.

The current project arose out of shared interests between Manoli and co-author and neurobiologist Nirao Shah, MD, PhD, then at UCSF and now at Stanford Medicine. Shah has been interested in the biology of oxytocin and social attachment in prairie voles since teaching about oxytocin studies decades earlier. Manoli, who wanted to investigate the neurobiology of social bonding, joined Shah’s lab in 2007 as a postdoctoral researcher.

In this study, which was 15 years in the making, the two applied novel genetic techniques to confirm whether oxytocin binding to its receptors was indeed the factor behind pair bonding. They used CRISPR to generate prairie mice that lack a functional oxytocin receptor. Next, they tested the mutant mice to see if they could form lasting partnerships with other mice.

To the researchers’ surprise, the mutant mice formed pair bonds as easily as normal mice.

“The patterns were indistinguishable,” said Manoli. “Major behavioral traits once thought to be dependent on oxytocin—sexual partners getting together and rejecting other potential partners as well as parenting by mothers and fathers—seem perfectly intact in the absence of their future.”

Labor and lactation

What was most surprising to Manoli and Shah of the pair bonding was the fact that a large proportion of the females were able to give birth and provide milk for their young.

It’s likely that oxytocin plays a role in both childbirth and lactation, Manoli said, but it’s a more subtle role than previously thought. Female rats without receptors have been shown to be fully capable of giving birth, in the same time frame and in the same manner as normal animals, despite the belief that labor is dependent on oxytocin.

The findings help clear up some of the mystery surrounding the hormone’s role in childbirth: Oxytocin is commonly used to induce labor, but blocking its action in mothers experiencing preterm labor is no better than other methods of stopping contractions.

When it came to producing milk and feeding the pups, the researchers were surprised. Binding of oxytocin to its receptors has been essential for milk expulsion and parental care for many decades, but half of the mutant females were able to successfully nurse and wean their pups, suggesting that oxytocin signaling plays a role, but it’s less important than previously thought.

“This upends the conventional wisdom about lactation and oxytocin that has been around for much longer than the bonding bond of pair,” Shah said. “It’s standard in the medical books that the hormone mediates the galactorrhea reversal, and behold, we say, wait a minute, there’s more to it than that.”

We hope to socialize

Manoli and Shah focused on understanding the neurobiology and molecular mechanisms of pair bonding because it is believed to be 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, much hope has been pinned on clinical trials using oxytocin to treat those conditions. But these results have been mixed, and none point to a clear path to improvement.

The researchers said their study strongly suggests that the current model — a single pathway or molecule responsible for social connection — is oversimplified. This conclusion, they said, makes sense from an evolutionary perspective, given the importance of the link in perpetuating many social species.

“These behaviors are too important for survival to depend on this single point of potential failure,” Manoli said. It is likely that there are other pathways or genetic wiring to allow for this behaviour. Oxytocin receptor signaling can be one part of this program, but it’s not all.”

See also

This discovery points the researchers down new paths to improving the lives of people who struggle to find social connection.

Shah said, “If we can find the main pathway that mediates attachment and bonding behavior, we will have an eminently addressable target for alleviating symptoms in autism, schizophrenia, and many other psychiatric disorders.”

Authors: Additional authors include: Ruchira Sharma, Rose Larios, Nastasia Goodwin, Michael Sherman and Isidro Espineda of the University of California, San Francisco, Maricruz Alvarado Mandujano, Yichao Wei, Srinivas Parthasarthy and Joseph Knodler of Stanford, Forrest Rogers, Trenton Simmons, Adelika Bond, Karen Bales of the University of California, Davis, and Annalize Perry of the University of California, Berkeley.

Funding: This work was supported by NIH Grants R01MH123513, R01MH108319, DP1MH099900 and R25MH060482, NSF Grant 1556974, and Philanthropy. For more details, see the study.

About this bonding and oxytocin research news

author: Robin Marx
Source: University of California, San Francisco
Contact: Robin Marks – UCSF
picture: The image is in the public domain

Original search:open access.
“The oxytocin receptor is not required for social bonding in prairie volesBy Devanand Manoli et al. nervous

Summary

The oxytocin receptor is not required for social bonding in prairie voles

Highlights

• voles that lack oxytocin receptors (Oxtr) was generated using CRISPR targeting
• Oxtr^{– / –} Folates form pair bonds or social bonds
• Oxtr^{– / –} Mice show parental behavior
• Oxtr^{– / –} Females nurse several of their young for weaning

summary

Mice are among a small group of mammals that exhibit long-term social bonding between mating partners. Several pharmacological studies show that signaling via the oxytocin receptor (Oxtr) is critical to displaying social monogamy in these animals. We used CRISPR mutants to generate three different variants Oxtr-null mutant foley prairie lines.

Oxtr Mutants showed a social correlation such that males and females showed a behavioral preference for their mating partners over a stranger of the opposite sex, even when assessed using different experimental settings.

Oxtr-deficient mothers gave birth to viable pups, and the parents showed care for their pups and raised them to the weaning stage.

Together, our studies unexpectedly reveal that social attachment, parturition, and parental behavior can occur in the absence of Oxtr signaling in prairie voles.