Prairie voles without oxytocin receptors can bond with mates and young

The important role of oxytocin – the “love hormone” – for social relationships is being questioned. More than 40 years of clinical and behavioral research have shown oxytocin receptor signaling as an important pathway for the development of social behavior in prairie voles, humans and other species, but a published genetic study in the newspaper. Neuron on January 27 shows that voles can create enduring bonds with partners and provide parental care without oxytocin receptor signaling.

Prairie voles are one of the few monogamous mammals. After mating, they form lifelong bonds known as “pair bonds.” Paired voles share parenting responsibilities, prefer the company of their mates over unknown members of the opposite sex, and actively reject potential new mates. Previous studies that used drugs to prevent oxytocin from binding to its receptor found that voles were unable to form bonds when oxytocin signaling was turned off.

Neuroscientists Devanand Manoli of UCSF and Nirao Shah of Stanford University wanted to know if the two relationships were actually controlled by oxytocin receptor signaling. To test this, they used CRISPR to generate prairie voles that lack functional oxytocin receptors. Next, they tested these voles without the mutant oxytocin to see if they could form lasting bonds with other voles. They were surprised when the mutant voles formed double bonds just as easily as the normal voles.

“We were all surprised that no matter how many different ways we tried to test this, the voles showed a strong bond with their sexual partner, just as strong as their normal partner. ,” says Manoli.

Next, the researchers wondered if oxytocin receptor signaling could be used in the same way for its other functions—separation, parenting (which, in prairie voles, is a shared responsibility between two parents), and the release of milk during lactation.

“We found that the mutant voles are not only unable to give birth, but actually lactate,” says Shah. Both male and female mutants engaged in standard parenting practices of touching, licking, and grooming, and were able to raise pups to weaning age.

However, the mutant prairie voles had a lower milk production compared to the normal voles. As a result, few pups survived to adulthood, and those that did were small compared to normal prairie voles. The fact that the voles were able to nurse at all contrasts with similar studies of oxytocin-receptor-deficient mice, which completely failed to nurse or nurse, and whose pups die within a day or so after birth.

The authors speculate that this species difference may be due to the biological nature of the laboratory mouse species rather than to different genetics. “It may be that reproduction in mice has chosen to rely heavily on oxytocin signaling, or this may represent a specific aspect of oxytocin receptor signaling,” says Shah.

When asked why their results differ from previously published studies that used drugs to block the signaling of oxytocin receptors, the authors point to an important difference between genetic studies and medicine: accuracy. “Drugs can be dirty,” says Manoli, “in the sense that they can bind to many receptors, and you don’t know which binding action is causing the effect. From a genetic point of view , we now know that the accuracy of removing this one receptor, and then eliminating its signaling pathways, does not interfere with these processes.”

“For at least the last 10 years, people have been hoping for the possibility of oxytocin as a powerful treatment for helping people with social disabilities due to conditions ranging from autism to schizophrenia,” Manoli says. “This study shows that there is probably no magic formula for something as complex and unusual as social behavior.”

Another important difference is that, while many pharmacological studies suppress oxytocin receptor signaling in adult animals, this study turned it off when the voles were embryos. “We’ve made a change that starts from before birth,” says Shah. “There may be compensatory or redundant pathways that enter these mutant animals and mask deficits in attachment, parental behavior and milk yield.”

Working with prairie voles has presented an obstacle, but one that must be overcome. Because prairie voles are not as commonly used in genetic studies as laboratory mice, the team needed to create all of their molecular tools and protocols from scratch. Now that they have the tubes and special vole equipment, the authors are excited about the doors opening, for themselves and for other researchers.

“We are very excited to be part of the community and have this technology to share,” says Manoli. “Now we have this trove to start with. There are many other questions that prairie voles can be interesting and helpful to answer, both in terms of potential clinical implications for models. of anxiety or attachment and for basic comparative biology.”