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A new animal study shows how the neuropeptide oxytocin specifically promotes social behavior. Researchers have demonstrated that oxytocin acts directly in the medial prefrontal cortex, a central area of the brain responsible for social behavior. There, it activates specific nerve cells that promote social interaction. It is noteworthy that this effect persists even under hunger. The results provide important insights into how sociability is modulated in the brain and why it can be maintained even under vital physiological demands, such as hunger.
The neuropeptide oxytocin is a special messenger substance that nerve cells use to communicate with each other. It is acting as both a neurotransmitter and a hormone and is best known for promoting social behavior. However, it remains largely unclear exactly which brain structures and cell types oxytocin affects during social behavior. In order to identify possible mechanisms in the brain, an international research team led by the Central Institute of Mental Health (CIMH) in Mannheim conducted an animal study, the results of which have now been published in the journal Nature Communications.
Direct oxytocin effect in the medial prefrontal cortex
Using optogenetic approaches, the researchers selectively evoked local oxytocin release from hypothalamic projections terminating in the infralimbic cortex. This spatially restricted release was sufficient to robustly increase social interaction in female rats. This is the first time that an oxytocin-sensitive cortical circuit promoting sociability has been dissected.
Special nerve cells promote social interaction
The researchers focused on cells with oxytocin receptors, which are predominantly inhibitory interneurons. Their function is to inhibit principal neurons. In other words, these cells suppress the activity of other cortical neurons, particularly those that project to the amygdala, a key region involved in fear and emotional processing.
“These inhibitory interneurons act as an amplifier for social signals in the medial prefrontal cortex,” explains Stephanie Schimmer, a member of the Neuropeptide Research Department in Psychiatry at the CIMH and the first author of the study. “When these cells are activated, they specifically increase the animals’ willingness to interact.”
Prosocial behavior remains despite hunger
It is particularly relevant that the prosocial effect persisted even under conditions of hunger. Normally, social needs compete with basic survival motives in such situations. “Our findings suggest the existence of a specialized neural circuit that supports social contact even when the organism is under competing physiological challenges, such as food deprivation,” says Prof. Dr. Valery Grinevich, head of the Department of Neuropeptide Research in Psychiatry at the CIMH and last author of the study.
Targeted inhibition of anxiety-related networks
Further analyses by the researchers showed that the activated interneurons primarily inhibit nerve cells that transmit signals to the amygdala, a center for fear and emotional evaluation. “This could be a possible explanation for how oxytocin selectively dampens anxiety-related processes and promotes social behavior,” says Grinevich.
He is convinced that a better understanding of the precise anatomical and cellular target structures of oxytocin will contribute to a better understanding of the neural basis of social behavior, empathy, trust, and social decision-making. Many mental illnesses, such as anxiety disorders, autism spectrum disorder, depression, and schizophrenia, are associated with changes in social behavior. Findings in this area can therefore make an important contribution to the development of effective therapies and the improvement of existing ones.
In addition to researchers from the CIMH, scientists from Heidelberg University Hospital, and universities in Strasbourg (France), Haifa (Israel), and Krakow (Poland) also participated in this study, initiated by Valery Grinevich at the Max Planck Institute for Medical Research in Heidelberg more than a decade ago.
Schimmer S, Kania A, Lefevre A, Afordakos K, Wang K-Y, Lebedeva J, et al. Oxytocin facilitates social behavior of female rats via selective modulation of interneurons in the medial prefrontal cortex. Nat Commun. 2026;17:1932. DOI:10.1038/s41467-026-68347-x.
https://doi.org/10.1038/s41467-026-68347-x
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