The receptor for the hormone oxytocin, which is thought to be crucial in establishing social bonds, may not be playing the important role scientists have attributed to it for the past 30 years, according to new research from UC San Francisco and Stanford Medicine researchers. This finding challenges decades-old dogma.
In the study, published in the journal Neuron, researchers discovered that shrews reproduce without oxytocin receptors and exhibit the same monogamous mating, attachment, and parenting behaviors as ordinary mice. Also, females lacking the oxytocin receptor gave birth and produced milk, although to a lesser extent than typical female voles.
The findings show that oxytocin receptors, popularly referred to as the "love hormone", are not the only biological factor that governs couple bonding and parenting.
While oxytocin is referred to as "Love Potion #9," psychiatrist Devanand Manoli, MD, Ph.D., one of the study's senior authors and a fellow of the UCSF Weill Institute for Neurosciences, suggested that potions 1 through 8 may be sufficient. “This study shows that oxytocin is probably just a small component of a much more complex genetic pathway.”
Field Mice with CRISPR
Researchers study prairie voles, one of the few mammalian species known to develop monogamous relationships throughout life, to learn more about the nature of social bonding.
In the 1990s, studies using drugs that inhibit the binding of oxytocin to its receptor showed that voles were unable to form a double bond. This led the researchers to conclude that the hormone is essential for the development of such relationships.
The current effort began as a result of the similar interests of Manoli and neurobiologist Nirao Shah, MD, Ph.D., now at Stanford Medicine. Since lecturing on oxytocin studies decades ago, Shah had a keen interest in oxytocin biology and social connectedness in prairie voles. Manoli joined Shah's group in 2007 as a postdoctoral researcher to study the neurology of social bonding.
The duo used the latest genetic technologies for this 15-year project to confirm whether the binding of oxytocin to its receptor is the cause of its double bond. They created prairie mice lacking working oxytocin receptors using CRISPR technology. The mutant mice were then tested to see if they could form long-term relationships with other mice.
The researchers were surprised that mutant voles formed double bonds as easily as normal voles.
Manoli observed that the patterns were indistinguishable. “In the absence of the oxytocin receptor, the primary behavioral traits that are presumed to be oxytocin-dependent – parenting by parents as well as sexual partner cuddling and rejection of other potential partners – appear to be completely intact.”
The fact that a significant proportion of female voles were able to give birth and produce milk for their young was even more shocking to Manoli and Shah than their pair bond. According to Manoli, oxytocin probably plays a more complex role in breastfeeding and childbirth than previously thought.
What You Didn't Know About Oxytocin
Despite the belief that birth is dependent on oxytocin, it has been proven that female mice without receptors can give birth in the same way as other animals and at the same time.
The findings contribute to a better understanding of the hormone's function in labor: While oxytocin is often used to induce labor, stopping its production is no more effective than using other methods for stopping contractions in very preterm mothers.
But the researchers were surprised at how the animals produced milk and fed their young.
Because oxytocin binding to its receptor has long been believed to be essential for lactation and parental care, the fact that half of mutant females are successful at suckling and weaning their offspring suggests that oxytocin signaling may still play a role, but may not be as important as previously believed.
According to Shah, this refutes long-held beliefs about oxytocin and breastfeeding that are much longer than couple bonding. Medical textbooks typically state that the hormone mediates the lactation reflex, but here we say, "Wait, there's more to it than that."
Manoli and Shah focused on understanding the neurobiology and molecular mechanics of pair bonding, as it is believed to hold the key to better treatments for psychiatric disorders such as autism and schizophrenia that impair a person's capacity to form or maintain social bonds.
Over the past decade, clinical trials using oxytocin to treat these disorders have been approached with great optimism. However, the results were inconsistent and none showed a definitive path for improvement.
According to the researchers, this study clearly demonstrates that the current hypothesis linking social connectedness to a single pathway or chemical is simple. From an evolutionary perspective, they argued, this conclusion makes sense given the importance of attachment to the survival of many social species.
“These behaviors are too important for survival to be tied to a single potential point of failure,” Manoli added. “There are probably more genetic circuits or pathways that allow this behavior. While oxytocin receptor signaling is a component of this program, it is not the only component.”
This finding leads researchers into new ways to help those who have trouble interacting socially.
Shah said: “If we can uncover the primary pathway that mediates attachment and attachment behavior, we will have a highly medicated target for alleviating symptoms in autism, schizophrenia and many other psychiatric disorders.
Günceleme: 29/01/2023 00:37
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