Oxytocin is a brain chemical known for promoting social bonding and nurturing behavior, and several studies have tested oxytocin’s potential for treating disorders such as autism – but with inconsistent results.

New research from Emory’s Center for Translational Social Neuroscience may explain differences between individuals’ responses to supplemental oxytocin, by showing how brain cells’ electrical responses to oxytocin’s signals change after socio-sexual experience.

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Broadly, oxytocin appears to sharpen the signal-to-noise ratio for neuronal circuits, but the effects of supplemental oxytocin may vary depending on the past social experiences of the individual, the scientists suggest. The results were published Feb. 1 in Current Biology.

“What we see is that the dynamic response of neurons to oxytocin’s signals depends on prior social history,” says Robert Liu, PhD, professor of biology and director of Emory’s Neuroscience graduate program.

For a vole, defensive posture means rejection by a partner. Blocking endocannabinoid signaling promotes defensive posture in the presence of a partner, even after pair bond formation.
Illustration by Marco S. Moreno, courtesy of Robert Liu

The study was conducted in female prairie voles, rodents that form lifelong bonds with their partners, in collaboration with Larry Young’s lab at Yerkes National Primate Research Center, Emory University. Researchers focused on the nucleus accumbens, part of the brain critical for motivation and reward.

Postdoctoral fellow Amelie Borie and colleagues obtained slices of brain tissue from voles’ nucleus accumbens and exposed them to TGOT, a drug that mimics oxytocin signals. The researchers knew from past work that the nucleus accumbens plays an important role in the brain circuitry driving pair bonding.

Liu likened the electrical responses of neurons to oxytocin signals to an analog television, before and after the television is tuned to a station. Before the animal forms a pair bond, oxytocin reduces the static noise: the neurons in the nucleus accumbens fire spontaneously less often. But after an animal has been exposed to a partner, it increases the clarity of the signal from the station: the neurons gradually fire with greater strength – but only when electrically triggered.

Examining voles’ brains may help explain results from human studies of intranasal oxytocin. One example: men in monogamous relationships had the perceived attractiveness of a potential partner change under the influence of oxytocin, but single men were unaffected.

Most studies on the effect of supplemental oxytocin in humans account for differences based on variations in receptor density – that is, some people’s brain cells may be more sensitive to oxytocin. But these results show that the neural response to oxytocin itself changes in character after long-term social experience.

“In the context of pair bonding, we didn’t have much of a picture of what oxytocin does at the electrophysiological level,” Liu says.

What was unexpected, he says, was how oxytocin signals become coupled to endocannabinoids, molecules produced within the brain that resemble the psychoactive substances found in cannabis products now on sale at the local CBD oil UK store. The scientists could interfere with some aspects of pair interactions in prairie voles by blocking endocannabinoids pharmacologically.

In female prairie voles that have already formed pair bonds, blocking endocannabinoid signals increases the likelihood that the vole will display a sign of rejection – defensive upright posture – in the presence of their partner, but not toward a stranger. However, the pair-bonded animals still spent more time with the partner than a stranger.

“We don’t know if they think the partner looks more like a stranger,” Liu says. “But their reaction is more like that of a stranger. It shows that endocannabinoid signaling is modulating defensive interactions, rather than pair bonding itself.”

Focusing on subtle interactions such as defensive posture – rather than physical proximity, a coarser gauge of pair bonding — could help scientists understand brain circuitry underlying social behaviors, he adds. Whether similar effects of oxytocin can be seen in male voles is still under investigation.

The research was supported by the National Institute for Mental Health (R01MH115831, P50MH100023) and the NIH Director’s Office of Research Infrastructure Programs (Primate centers, P51OD011132).