Studies Show That the Biology Underlying Pair Bonding and Parenting May Not be Dictated by Oxytocin Receptors

New research from scientists at UC San Francisco and Stanford Medicine is changing decades-old dogma and suggesting that oxytocin receptors, a hormone thought to be important in forming social bonds, may not play the crucial role that scientists attribute to them. last 30 years.

In a study published in Neuron on Jan. 27, 2023, the team found that prairie voles without oxytocin receptors reproduced and exhibited the same mating, attachment, and monogamous parenting behaviors as normal mice. In addition, females without oxytocin receptors gave birth and produced milk, albeit in smaller amounts, than female rats.

The results suggest that the biology underlying pair bonding and parenting is not solely dictated by oxytocin receptors, sometimes dubbed the “love hormone.”

The CRISPR mouse surprised us

Because the prairie mouse is one of the few mammalian species known to form lifelong monogamous relationships, the researchers studied them to better understand the biology of social bonds.

Studies in the 1990s using a drug that prevented oxytocin from binding to its receptors found that rats were unable to bind, leading to the assumption that the hormone was important in forming such a bond .

The current project grew out of a shared interest between Manoli and co-senior author and neurologist Nirao Shah, MD, PhD, then at UCSF and now at Stanford Medicine. Shah has been interested in oxytocin biology and social bonding in prairie voles since he had taught the study of oxytocin several decades earlier. Manoli joined Shah’s lab in 2007 as a postdoctoral researcher who wants to study the neurobiology of social bonding.

For this study, which took 15 years to complete, the pair used new genetic engineering to determine if oxytocin’s binding to its receptors was in fact the factor behind pair bonding. They used CRISPR to create prairie mice that lacked functional oxytocin receptors. Then 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 just as easily as normal mice.

“The patterns are indistinguishable,” says Manoli. “Key behavioral traits thought to be dependent on oxytocin — sexual partners huddled together and rejection of other potential mates and maternal and paternal care — appear to be fully intact in the absence of its receptors.”

Labor and lactation

Even more surprising to Manoli and Shah than the pair’s bond was the fact that most female rats are capable of bearing and lactating their young.

Oxytocin likely plays a role in childbirth and breastfeeding, but one that’s more nuanced than previously thought, Manoli said. Female mice lacking the receptor were found to be highly capable of giving birth in the same timeframe and manner as normal animals, although the parturition process was thought to be oxytocin-dependent.

The results help clear up some of the mysteries surrounding the role of hormones in labor: Oxytocin is commonly used to induce labor, but blocking its activity in mothers in preterm labor is no better than other approaches to stopping labor.

However, when it came to milk production and feeding the puppies, the researchers were surprised. Oxytocin binding to its receptors has been thought to be important for milk flow and parental care for decades, but half of the mutant females have successfully nursed and weaned their young, suggesting that oxytocin signaling plays a role, but less importance is than before. thought.

“This turns on its head the conventional wisdom about lactation and oxytocin, which has been around for much longer than the attachment relationship,” says Shah. “It’s standard in medical textbooks that the milk ejection reflex is hormone mediated, and here we say, ‘Wait a minute, there’s more to it.'”

Expectations of social relationships

Manoli and Shah focused on understanding the neurobiology and molecular mechanisms of pair bonding because they are thought to hold the key to unlocking better treatments for psychiatric disorders like autism and schizophrenia, which impair a person’s ability to form or maintain social bonds.

In the past decade, much hope has been placed on clinical trials of oxytocin to treat this condition. But these results were mixed, and none showed a clear path for improvement.

The researchers say their study overwhelmingly shows that the current model — a single pathway or molecule responsible for social bonding — is oversimplified. This conclusion makes sense from an evolutionary perspective, they say, given the importance of attachment to the survival of many social species.

“This behavior is too important for survival to depend on this one potential failure point,” says Manoli. “There may be other pathways or other genetic connections that allow this behavior. Oxytocin receptor signaling might be part of the program, but it’s not the end.”

The findings lead researchers to new ways to improve the lives of people who struggle to find social connections.

“If we can find the major pathways that mediate attachment and attachment behaviors,” says Shah, “we have a highly anesthetic goal to reduce the symptoms of autism, schizophrenia, and many other psychiatric disorders.”