Lack of oxytocin may not prevent bonding, but why?

• Previous studies on the role of oxytocin in social bonding used drugs to block the oxytocin receptor, but researchers have now used genetic technology to generate prairie voles that lack functional oxytocin receptors.
• Surprisingly, these mutant prairie voles still displayed the behavioral traits thought to be dependent on oxytocin, namely pair bonding and parental care.
• A better understanding of the role of oxytocin in social attachments is required, but the researchers believe that their new genetic model will facilitate future research.

Oxytocin is a hormone produced by the brain. For more than 30 years, research has indicated that oxytocin is involved in the formation of social and emotional bonds in humans, prairie voles, and other species. This is why oxytocin is also known as “the love hormone.”

Animal model studies have shown that the binding of oxytocin molecules to specific receptors in the brain, called “oxytocin receptor signaling,” drives pair-bonding behavior — the formation of strong relationships between monogamous partners.

Oxytocin receptor signaling is also thought to control parental care of young and milk ejection in response to suckling.

Now, new research from the University of California and Stanford University is challenging these long-accepted beliefs.

Dr. Devanand Manoli, senior author of the study and assistant professor of psychiatry at the University of California San Francisco, notes that he and his team “were all shocked that no matter how many different ways we tried to test this, the voles demonstrated a very robust social attachment with their sexual partner, as strong as their normal counterparts.”

The results of their study appear in the journal Neuron.

Researchers studying the role of oxytocin in social bonding have often used prairie voles in their studies because these rodents are known to be monogamous.

Partner voles spend time nestled closely together and show a distinct preference for each other over other potential mates. This pair-bonding behavior is uncommon in the animal world. Prairie voles also exhibit bi-parental care of vole pups.

Yet prairie voles are not commonly used in genetic studies in the same way as mice. This meant that Dr. Manoli and coworkers had to develop new tools and protocols to generate prairie voles that lack functional oxytocin receptors.

They used a revolutionary gene editing technology called CRISPR — which stands for “Clustered Regularly Interspaced Short Palindromic Repeats” — that allows scientists to precisely target and manipulate specific genes within an organism’s DNA.

The researchers sought to determine if the mutant voles exhibit impairments in pair bonding by housing sexually inexperienced males and females together for 7 days, which has previously been demonstrated to be sufficient for establishing pair bonds. They also observed the prairie voles’ ability to provide parental care for their offspring.

When male and female prairie voles without oxytocin receptors were exposed to unfamiliar, non-mutant control voles they spent more time huddling with their partners.

They also displayed aggression toward the unfamiliar members of the opposite sex, indicating rejection of other potential mates.

Like normal prairie vole parents, mutant parents spent the majority of their time in the nest, in direct contact with their litters, and, in the case of mothers, nursing pups.

However, the pups born to mutant mothers weighed significantly less at weaning than pups born to normal mothers, indicating a potential issue with milk ejection or a slight deficiency in nursing behavior.

In the study report, the authors point out that their findings were consistent across three laboratories.

Dr. Larry J. Young, William P. Timmie professor of psychiatry and director of the Silvio O. Conte Center for Oxytocin and Social Cognition at Emory University, told MNT:

“These results were surprising to me because previous research in my lab and others ha[s] clearly shown that oxytocin receptor signaling [is] important for pair bonding in normal adult prairie voles. […] I believe their results because we have also created […] voles [without oxytocin receptors] and obtained similar results which are not yet published.”

Dr. Young believes that prairie voles have “hard-wired circuits for pair bonding.” Normal prairie voles experience oxytocin release during social situations, and their circuits become dependent on oxytocin.

On the other hand, prairie voles without oxytocin receptors never experience oxytocin release, and although their pair-bonding circuits still exist, they are not regulated by oxytocin.

“If you cover someone’s eyes, they cannot read,” said Dr. Young. “However, if someone is blind from birth, there are changes in neural circuits so that they develop very sensitive somatosensory systems and they can read braille.”

“So perhaps if an animal never experiences oxytocin, i[t] can use some other processes to facilitate social interactions and bonding, but in a complex situation it may not be as strong and efficient as in a wildtype,” he hypothesized.

Although the behavior of the mutant voles appears normal in a lab setting, Dr. Young expects that “in the wild, there would be nuanced differences that may make the [mutant voles] socially awkward and possibly unable to bond.”

Prof. Donatella Marazziti, a professor of psychiatry at the University of Pisa in Italy, not involved in the current study, hypothesized that the phenomenon may have something to do with the relationship between oxytocin and vasopressin, which also contributes to social bonding and parental care, according to existing research.

“We do […] know that oxytocin interacts with vasopressin receptors, and maybe some subtypes of these might replace the oxytocin ones,” Prof. Marazziti suggested.

Based on observations in prairie voles and other mammals including humans, clinical trials have used oxytocin to improve social attachment behavior in individuals with certain psychiatric conditions.

Researchers have also administered oxytocin to some children on the autism spectrum, but these studies have produced mixed results.

While Dr. Manoli and coauthors hypothesize that their findings may explain these inconsistent results, Dr. Young disagrees.

“The reason for the [oxytocin clinical trial] failures has to do with poor penetration of the oxytocin into the brain after sniffing, and the fact that oxytocin needs to be paired with behavioral therapy, which most studies do not do,” he told MNT. 

Prof. Marazziti also strongly expressed caution in interpreting the study’s findings. “My opinion [is] that it might be difficult and dangerous, albeit sensational, to cloud and delete decades of converging data on the role of oxytocin in mating and bonding,” she told us.

Still, she acknowledged that the study’s findings may warrant further investigation: “Although I would recommend caution before drawing any conclusions, nevertheless, it also true that a paper not aligned to common paradigms may be a challenge and cannot be neglected.”

Overall, the study reveals the need for a deeper understanding of the molecular processes behind social attachment behaviors. The authors speculate that oxytocin-blocking substances used in earlier research might have impacted yet-undiscovered pathways that play a role in pair bonding.

Dr. Manoli anticipates that innovative genetic models, such as the oxytocin receptor-lacking prairie voles generated in this study, will enable a more thorough examination of the molecular and circuit mechanisms that regulate attachment behavior and its impairment in patients with neuropsychiatric disorders.

Source: Read Full Article