It was believed that the hormone is important for the formation of social bonds between animals.
Meadow voles have long been considered a model of monogamy. Now, research suggests that the “love hormone” once thought essential to their bond — oxytocin — may not be so essential.
Interest in the romantic life of meadow voles ( Microtus ochrogaster ) first emerged more than 40 years ago, says Devanand Manoli, a biologist at the University of California, San Francisco. Biologists trying to capture voles for study often caught two at a time because “what they were finding were female-female pairs,” he says. Unlike many other rodents with their multiple partners, meadow voles have been shown to mate for life.
Meadow voles, which are paired, prefer each other’s company to that of a stranger, and like to huddle together both in the wild and in the laboratory. Because other vole species do not have the complex social behavior of meadow voles, they have been a popular animal system for studying the evolution of social behavior.
Research over the past few decades has shown that certain hormones in the brain are vital for proper vole manners, especially oxytocin, which is also important for social behavior in humans and other animals.
Manoli and his colleagues believed that the oxytocin receptor, a protein that detects and responds to oxytocin, would be an ideal test target for a new genetic engineering method based on CRISPR technology, which uses bacterial molecules to selectively turn off genes. The researchers used this technique on vole embryos to create animals that were born without functioning oxytocin receptors. The team hypothesized that the rodents would be unable to form pair bonds, just like voles in past experiments in which oxytocin activity was blocked with drugs.
Instead, Manoli says, the researchers got a “big surprise.” Voles could form pair bonds even without oxytocinin reports the team in Neuron .
“I was very surprised by their results,” says Larry Young, a biologist at Emory University in Atlanta who was not involved in the study but has studied oxytocin in meadow voles for decades.
A key difference between the new study and past studies that used drugs to block oxytocin is when exactly the hormone shuts off. With the drugs, the voles are adults and have been exposed to oxytocin in their brains before shutting down. With CRISPR, “these animals are born without oxytocin signals in the brain,” says Yang, whose research team recently replicated Manoli’s experiment and got the same result.
Perhaps, Yang said, the bond between couples is controlled by a brain circuit that normally becomes dependent on oxytocin through exposure to it during development, like a symphony trained by a conductor. Suddenly remove that conductor and the symphony sounds dissonant, whereas a jazz orchestra that has never practiced with a conductor is fine without one.
Manoli agrees that the timing of the technique matters. A secondary reason for the discrepancy, he said, may be that the drugs often have off-target effects, for example, chemicals designed to block oxytocin could have other actions in the voles’ brains, affecting pair bonding. But Young disagrees. “I don’t believe it,” he says. “[Препарат]which humans use, is highly selective,” without even binding to the receptor for oxytocin’s closest molecular relative, vasopressin.
Does this result mean that decades of past work on pair bonding has been reversed? Not at all.
“This shows us that this is a much more complex issue,” says Manoli. “Pharmacological manipulations … showed that [окситоцин] plays a decisive role. The question is, what kind of role is it?”
The new, seemingly impressive result makes sense when you look at the big picture, Manoli says. The ability of voles to mate is “so important to the survival of the species,” he said. “From a genetics point of view, maybe it makes sense that there is no single point of failure.”
The team now hopes to investigate how other hormones, such as vasopressin, affect pair bonding using this relatively new genetic technique. They’re also taking a closer look at the voles’ behavior to make sure CRISPR gene editing hasn’t changed them in ways they haven’t already noticed.
In the game of “love” it feels like we’re still trying to figure out all the players.
