A Rehovot Study of Mice Shows How the ‘Love Hormone’ can Trigger Aggression as Well as Friendliness

Then Shimshon‘s wife harassed him with tears, and she said, “You really hate me, you don’t love me. You asked my countrymen a riddle, and you didn’t tell me the answer.” He replied, “I haven’t even told my father and mother; shall I tell you?” Judges 14:15

Oxytocin, popularly known as the “love hormone,” is produced by the hypothalamus in the brain and secreted by the pituitary gland, a pea-sized structure at the base of the brain. It has positive physical and psychological effects, including influencing social behavior and emotion. because it arouses feelings of affection and attachment. 

When a baby sucks at its mother’s breast, oxytocin secretion causes the milk to release so the baby can feed. It promotes contraction of the uterus during childbirth, the bonding between a mother and her newborn baby and between couples. It can also relieve pain. While less important in men, it affects sperm production. 

The fact that the hormone, whose name comes for the Greek words for “swift childbirth,” causes contraction o the uterus was discovered in 1906 by British pharmacologist Sir Henry Hallett Dale and its milk ejection property was described by various researchers a few years later.   

But oxytocin’s role is not all positive. During the pandemic lockdown, as couples have been forced to spend days and weeks in one another’s company, some have found their love renewed while others are on their way to divorce court. Researchers at the Weizmann Institute of Science in Rehovot have discovered for the first time that the neuromodulator may not only bring hearts together but that it can also help trigger aggression. 

Prof. Alon Chen’s lab group in the institute’s neurobiology department launched eight years ago an experimental setup that enabled them to observe mice in something approaching their natural living conditions – an environment enriched with stimuli they can explore. Their activity has been monitored day and night with cameras and analyzed computationally. The present study, led by research students Sergey Anpilov and Noa Eren, and staff scientist Dr. Yair Shemesh, has just been published in the prestigious journal Neuron. They believe the results could shed new light on efforts to use oxytocin to treat a variety of psychiatric conditions from social anxiety and autism to schizophrenia. 

Much of what we know about the actions of neuromodulators like oxytocin comes from behavioral studies of lab animals in standard lab conditions. These conditions are strictly controlled and artificial, in part so that researchers can limit the number of variables affecting behavior. But a number of recent studies suggest that the actions of a mouse in a semi-natural environment can teach us much more about natural behavior, especially when we mean to apply those findings to humans. 

The innovation in the Weizmann experiment, however, was to incorporate optogenetics – a method that enables researchers to turn specific neurons in the brain on or off using light. To create an optogenetic setup that would enable the team to study mice that were behaving naturally, the group developed a compact, lightweight, wireless device with which the scientists could activate nerve cells by remote control. 

With the help of optogenetics expert Prof. Ofer Yizhar of the same department, the group introduced a protein previously developed by Yizhar into the oxytocin-producing brain cells in the mice. When light from the wireless device touched those neurons, they became more sensitized to input from the other brain cells in their network. 

“Our first goal,” said Anpilov, “was to reach that ‘sweet spot’ of experimental setups in which we track behavior in a natural environment, without relinquishing the ability to ask pointed scientific questions about brain functions.” 

Shemesh added that “the classical experimental setup is not only lacking in stimuli, the measurements tend to span mere minutes, while we had the capacity to track social dynamics in a group over the course of days.” 

Examining the role of oxytocin was sort of a test drive for the experimental system. It had been believed that this hormone mediates pro-social behavior. But findings have been conflicting, and some have proposed another hypothesis, termed “social salience” stating that oxytocin might be involved in amplifying the perception of diverse social cues, which could then result in pro-social or antagonistic behaviors, depending on such factors as individual character and their environment. 

To test the social salience hypothesis, the team used mice in which they could gently activate the oxytocin-producing cells in the hypothalamus, placing them first in the enriched, semi-natural lab environments. To compare, they repeated the experiment with mice placed in the standard, sterile lab setups. 

In the semi-natural environment, the mice at first showed increased interest in one another, but this was soon accompanied by a rise in aggressive behavior. In contrast, increasing oxytocin production in the mice in classical lab conditions resulted in reduced aggression. “In an all-male, natural social setting, we would expect to see belligerent behavior as they compete for territory or food,” recalled Anpilov. “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.” 

Therefore, the “love hormone” is more likely a “social hormone.”  “Oxytocin is involved, as previous experiments have shown, in such social behaviors as making eye contact or feelings of closeness,” noted Eren, “but our work shows it does not improve sociability across the board. Its effects depend on both context and personality.” This implies that if oxytocin is to be used therapeutically, a much more nuanced view is needed in research: “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,” she concluded.