It seems that oxytocin is two-faced. The hormone that promotes feelings of love, social bonding, and well-being can also cause emotional pain, an entirely new, darker identity for the much studied hormone. The new findings, by researchers from Northwestern University, come from two experiments detailed in the journal Nature Neuroscience.
In the first experiment, three groups of mice were individually placed in cages with aggressive mice and experienced social defeat, a stressful experience for them. One group was missing its oxytocin receptors, essentially the plug by which the hormone accesses brain cells. The lack of receptors means oxytocin couldn’t enter the mice’s brain cells. The second group had an increased number of receptors so their brain cells were flooded with the hormone. The third control group had a normal number of receptors.
Six hours later, the mice were returned to cages with the aggressive mice. The mice that were missing their oxytocin receptors didn’t appear to remember the aggressive mice and show any fear. Conversely, when mice with increased numbers of oxytocin receptors were reintroduced to the aggressive mice, they showed an intense fear reaction and avoided the aggressive mice.
In the second experiment, the three groups of mice were again exposed to the stressful experience of social defeat in the cages of other more aggressive mice. This time, six hours after the social stress, the mice were put in a box in which they received a brief electric shock, which startles them but is not painful. Then 24 hours later, the mice were returned to the same box but did not receive a shock.
The mice missing their oxytocin receptors did not show any enhanced fear when they re-entered the box in which they received the shock. The second group, which had extra oxytocin receptors showed much greater fear in the box. The third control group exhibited an average fear response.
The findings surprised the researchers, who were expecting oxytocin to modulate positive emotions in memory, based on its long association with love and social bonding. “Oxytocin is usually considered a stress-reducing agent based on decades of research,” said researcher Yomayra Guzman. “With this novel animal model, we showed how it enhances fear rather than reducing it.”
“This experiment shows that after a negative social experience the oxytocin triggers anxiety and fear in a new stressful situation,” added co-researcher Jelena Radulovic. “That’s because the hormone actually strengthens social memory in one specific region of the brain.”
The brain region known as the lateral septum is where oxytocin strengthens negative social memory and future anxiety by triggering an important signaling molecule – ERK (extra cellular signal regulated kinases) – that becomes activated for six hours after a negative social experience. ERK causes enhanced fear, Radulovic believes, by stimulating the brain’s fear pathways, many of which pass through the lateral septum. The region is involved in emotional and stress responses.
The findings are important because chronic social stress is one of the leading causes of anxiety and depression, while positive social interactions enhance emotional health. The research is particularly relevant because oxytocin is currently being tested as an anti-anxiety drug and as a treatment for autism. “By understanding the oxytocin system’s dual role in triggering or reducing anxiety, depending on the social context, we can optimize oxytocin treatments that improve well-being instead of triggering negative reactions,” said Radulovic.
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