Although the hormone oxytocin is well-known for its ability to promote feelings of love, social bonding and well-being, new Northwestern Medicine research shows that oxytocin can also intensify painful emotional memories.
The findings are important as chronic social stress is strongly linked to anxiety and depression, and positive social interactions are known to enhance emotional health. The research, which was conducted on mice, is significant because oxytocin currently is being tested as an anti-anxiety drug in several clinical trials.
According to the study, oxytocin seems to play a major role in turning a stressful social situation into a long-term, painful emotional memory.
For example, when a social experience is negative or stressful, oxytocin activates a part of the brain that intensifies the memory and increases the likelihood of feeling anxious during future stressful events.
It is also thought that oxytocin intensifies positive social memories and, thereby, increases feelings of well-being, but that research is ongoing.
“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 Jelena Radulovic, M.D., Ph.D., the senior author of the study and the Dunbar Professsor of Bipolar Disease at Northwestern University Feinberg School of Medicine.
This is the first study to link oxytocin to social stress and its ability to amplify anxiety and fear during future stressful events. Northwestern scientists also identified the brain region responsible for these effects—the lateral septum—and the pathway or route oxytocin uses in this area to enhance negative emotions.
The researchers found that oxytocin intensifies negative social memory and future anxiety by triggering an important signaling molecule, called ERK (extracellular signal regulated kinases). This molecule becomes activated for six hours after a negative social experience.
ERK enhances fear, Radulovic believes, by stimulating the brain’s fear pathways, many of which pass through the lateral septum. This region of the brain is involved in emotional and stress responses.
The findings surprised the researchers, who were expecting oxytocin to influence 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 Yomayra Guzman, a doctoral student in Radulovic’s lab and the study’s lead author. “With this novel animal model, we showed how it enhances fear rather than reducing it and where the molecular changes are occurring in our central nervous system.’
In one experiment, three groups of mice were individually placed in cages with aggressive mice in which they experienced social defeat — a stressful experience for them. One group was missing its oxytocin receptors, the second group had an increased number of receptors so their brain cells were flooded with the hormone, and a 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 seem to remember the aggressive mice and showed no 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.
The paper was published in Nature Neuroscience.
Source: Northwestern University