HQ Team
January 30, 2023: The receptor of Oxytocin, a hormone considered essential to forming social bonds, may not play the role that scientists have assigned it for the past 30 years, according to US scientists.
A team of scientists at UC San Francisco and Stanford Medicine found that mouselike prairie voles, bred without receptors for Oxytocin, showed the same monogamous mating, attachment, and parenting behaviours as common voles.
Oxytocin is produced in the hypothalamus of the brain. It is released into the blood by the pituitary gland or to other parts of the brain and spinal cord, where it binds to oxytocin receptors to influence behaviour and physiology.
Prairie voles are one of the few mammalian species known to form lifelong monogamous relationships, and researchers study them to understand the biology of social bonding better.
In the study on January 27, 2023, in Neuron, the team concluded that females without oxytocin receptors gave birth and produced milk, though in smaller quantities than ordinary female voles.
‘Love hormone’
The results indicated that the receptors don’t purely dictate the biology underlying pair bonding and parenting for Oxytocin, sometimes referred to as the “love hormone.”
“While oxytocin has been considered ‘Love Potion #9,’ it seems that potions 1 through 8 might be sufficient,” said psychiatrist Devanand Manoli, PhD, a senior author of the paper and member of the UCSF Well Institute for Neurosciences. “This study tells us that oxytocin is likely just one part of a much more complex genetic program.”
The scientists used CRISPR to generate prairie voles that lack functional oxytocin receptors. Then, they tested the mutant voles to see whether they could form enduring partnerships with other voles. To the researchers’ surprise, the mutant voles formed pair bonds just as readily as normal voles.
CRISPR is a gene editing technology. The essence of CRISPR is simple: it’s a way of finding a specific bit of DNA inside a cell. After that, it alters that piece of DNA. CRISPR has also been adapted to turn genes on or off without changing their sequence.
There were ways to edit the genomes of some plants and animals before the CRISPR method was unveiled in 2012, but it took years and cost hundreds of thousands of dollars. CRISPR made it cheap and easy.
Behavioural traits
“The patterns were indistinguishable,” said Manoli. “The major behavioural traits that were thought to be dependent on oxytocin – sexual partners huddling together and rejecting other potential partners as well as parenting by mothers and fathers – appear to be completely intact in the absence of its receptor.”
A significant percentage of the female voles could give birth and provide milk for their pups.
Oxytocin binding to its receptor has been considered essential for milk ejection and parental care for decades. Still, half of the mutant females could nurse and wean their pups successfully, indicating that oxytocin signalling plays a role, but it is less vital than previously thought.
“This overturns conventional wisdom about lactation and oxytocin that’s existed for much longer than the pair bonding association,” said co-senior author and neurobiologist Nirao Shah, MD, PhD, PhD, at Stanford Medicine. “It’s a standard in medical textbooks that the hormone mediates the milk letdown reflex, and here we are saying, ‘Wait for a second, there’s more to it than that.”
Psychiatric conditions
The scientists focused on understanding the neurobiology and molecular mechanisms of pair bonding because it is thought 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.
According to the researchers, the current model – a single pathway or molecule responsible for social attachment –is oversimplified. They said this conclusion makes sense from an evolutionary perspective, given the importance of attachment to the perpetuation of many social species.
“These behaviours are too important to survival to hinge on this single point of potential failure,” said Manoli. “There are likely other pathways or another genetic wiring to allow for that behaviour. Oxytocin receptor signalling could be one part of that program, but it’s not the be-all-end-all.”
The discovery points the researchers down new paths to improving the lives of people struggling to find a social connection.
“If we can find the key pathway that mediates attachment and bonding behaviour,” Shah said, “We’ll have an eminently druggable target for alleviating symptoms in autism, schizophrenia, and many other psychiatric disorders.”
