Oxytocin’s Paradox: The “Love Hormone” Can Fuel Aggression

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The potential use of intranasal oxytocin for the treatment of social deficits associated with autism spectrum disorder (ASD) or in patients with other psychiatric disorders that involve social impairments is controversial and hotly debated.

Although some research suggests that intranasal oxytocin treatment (OT) may improve social deficits (Parker et al., 2017), there is a growing consensus that oxytocin's therapeutic potential is unpredictable. OT seems to have different outcomes based on situational environments and various individual factors that remain unclear. The bottom line: Not everyone responds the same way to intranasal oxytocin all the time and in every context.

About a decade ago, researchers started sounding alarm bells that oxytocin—often referred to colloquially as the "love hormone" or "cuddle chemical"—isn't only a "warm and fuzzy" molecule that universally promotes magnanimous, lovey-dovey behavior in every social context.

Two of the earliest studies on the so-called "dark side" of oxytocin found that the same hormone that has the power to promote social bonding and prosocial behaviors also appeared to promote ethnocentrism (De Dreu et al., 2011) and group-serving dishonesty (Shalvi & De Dreu, 2014).

This landmark research by Carsten de Dreu and colleagues suggests that oxytocin can be viewed as a double-edged sword. On the one hand, it seems to promote loyalty and fortify camaraderie between members of the same in-group; this can result in an uptick of prosocial behaviors toward one another if you are all part of the same family or tribe. On the flip side, oxytocin-induced social bonds also have the potential to reinforce ethnocentric tribalism and an "us" against "them" combativeness between members of in-groups and out-groups. (See "The Dark Side of Oxytocin" by Christopher Badcock.)

A few years ago, another study (Duque-Wilckens et al., 2018) identified that oxytocin receptors in a particular part of the brain called the bed nucleus of the stria terminalis (BNST) promoted social avoidance behaviors in female California mice when they were in an unfamiliar or threatening social context.

Taken together, these findings on the antisocial, agonistic, and "cold prickly" side of oxytocin gave rise to a "social salience" hypothesis, which posits that oxytocin can enhance the salience of both positive and negative social interactions depending on a variety of contextual elements and individual characteristics, including gender.

One of the key contextual elements that appears to influence whether oxytocin boosts "warm fuzzies" or "cold pricklies" has to do with the environment being cooperative and familiar or competitive and unfamiliar.

Oxytocin Neurons Can Elevate Both Prosocial and Agonistic Behaviors

A new, in-press paper (Anpilov et al., 2020) that will appear in the August 19 issue of Neuron offers optogenetics-based support for the social salience hypothesis of oxytocin neuromodulation. This study by researchers at Israel's Weizmann Institute of Science found that activating specific oxytocin neurons using optogenetics can elevate either prosocial or aggressive behavior in male mice depending on their environment and social context.

"Our work shows [that oxytocin] does not improve sociability across the board. Its effects depend on both context and personality," lead co-author Noa Eren said in a June 15 news release. "This implies that if oxytocin is to be used therapeutically, a much more nuanced view is needed in research."

For this somewhat nuanced study, the researchers used a wireless optogenetic device to stimulate the same oxytocin neurons in two very different environments. First, a group of male mice were placed in an unfamiliar environment that was complex, enriched, and designed to resemble the natural world. In this context, the mice initially displayed a heightened level of interest in one another.

However, in this semi-natural environment, the dynamics quickly turned aggressive when the researchers used their wireless optogenetic device to "turn on" oxytocin neurons in a brain region called the paraventricular hypothalamic nucleus (PVN). Conversely, in the second phase of the experiment, when the mice were in a sterile lab environment that was familiar and wasn't complex or enriched, stimulating the same oxytocin neurons resulted in friendly, prosocial behavior towards other mice.

"In an all-male, natural social setting, we would expect to see belligerent behavior as they compete for territory or food," lead co-author Sergey Anpilov said in the news release. "That is, the social conditions are conducive to competition and aggression. In the standard lab setup, a different social situation leads to a different effect for the oxytocin."

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The latest oxytocin findings (2020) from the Weizmann Institute support the social salience hypothesis of oxytocin based on a cohort of all-male mice. That said, the researchers note that future research should investigate if wireless optogenetic stimulation of PVN oxytocin neurons has the same effect on female mice.

Although we are beginning to understand the paradoxical nature of oxytocin, more research is needed. "If we want to understand the complexities of behavior, we need to study behavior in a complex environment. Only then can we begin to translate our findings to human behavior," Eren concluded.