The messenger oxytocin, known as the cuddle hormone, is known to promote social interactions in humans and animals. However, what exactly is going on in the brain has so far been unclear. Researchers have now uncovered the neural circuits involved in rats in detail. Accordingly, the messenger substance works directly in the prefrontal cortex, which plays an important role in emotional regulation and social behavior. At the same time, oxytocin dampens the transmission of signals to the amygdala, which is active in times of fear and stress. This means that the prosocial effects of the cuddle hormone are maintained even in the face of hunger and other essential needs.
The neurotransmitter oxytocin works in many ways in the body and brain. It is considered a key factor for interpersonal relationships – from the mother-child bond to friendships and couple relationships. Because it is released, among other things, during loving physical contact with other people, it is also known as the “cuddle hormone”. Oxytocin promotes empathy and trust, relieves fear and pain, and lowers heart rate and blood pressure. How exactly it works in the brain was still unclear.
Attenuation of stress signals
A team led by Stephanie Schimmer from the Central Institute for Mental Health in Mannheim has now used rats to demonstrate which neuronal circuits oxytocin promotes social behavior. To do this, the researchers first examined the brains of dead and living rats using various methods and made visible which nerve cells the messenger substance binds to. It was shown that oxytocin acts directly in the medial prefrontal cortex – a region of the cerebrum that is associated, among other things, with emotional regulation and social behavior.
According to the results, most oxytocin receptors are located on so-called inhibitory interneurons. These intermediate nerve cells dampen the activity of other, downstream nerve cells. In the case of oxytocin, the interneurons activated by the messenger ensure that downstream nerve cells transmit fewer signals to the amygdala, a brain region that is associated with fear and stress and is responsible, among other things, for the release of stress hormones. “This could explain how oxytocin specifically dampens anxiety-related processes and promotes social behavior,” says Schimmer’s colleague Valery Grinevich.
Eating or social contact?
In further experiments, the researchers directly tested how oxytocin affects the behavior of rats. To do this, they specifically increased the oxytocin level in the animals’ cerebrums, partly by injection and partly using optogenetic methods, in which irradiation of certain areas of the brain leads to the local release of the messenger substance. When the rats manipulated in this way were placed with other rats, they spent significantly more time sniffing their counterparts and seeking physical contact. However, the animals did not show any increased interest in a toy rat as a substitute for a living counterpart, even with increased oxytocin release.
The prosocial effect continued even when the rats were given the choice between interacting with an unfamiliar rat or eating after 24 hours without food. Without additional oxytocin, most starving animals chose the food. When the oxytocin level was artificially increased, they preferred social interaction. “Our results suggest that a special neural circuit maintains social contact even when the body is stressed by competing physical needs such as hunger,” says Grinevich.
From the researchers’ perspective, the results can contribute to a better understanding of the neural basis of social behavior, empathy, trust and social decision-making. Understanding the signaling pathways involved could even help develop new therapies for mental illnesses such as anxiety disorders, autism spectrum disorder, depression or schizophrenia, which are associated with problems in social behavior.
Source: Stephanie Schimmer (Central Institute for Mental Health, Mannheim) et al., Nature Communications, doi:10.1038/s41467-026-68347-x.