Researchers at São Paulo State University (UNESP) in Brazil have demonstrated in rats that a synthetic version of oxytocin can prevent anxiety-related behaviors caused by social stress. The study was published in the journal Progress in Neurobiology and reinforces the role of oxytocin and the neural circuits associated with it in modulating anxiety. It also paves the way for new therapeutic approaches.
"We observed that, after a series of experiments generating social stress in male rats, carbetocin [a synthetic oxytocin analog] had a preventive effect on this type of anxiety," explains Carlos Crestani , a professor at the Faculty of Pharmaceutical Sciences of Araraquara (FCFAr-UNESP) and coordinator of the study, which was supported by FAPESP . "The dose used had no anxiolytic effect, i.e., it didn't make the animal more courageous. What happened was that it behaved similarly to the animals in the control group, which didn't undergo stress," he adds.
Oxytocin, known as the hormone of love and well-being, has an inverse relationship with cortisol, which is involved in various stress-related pathologies. While the cortisol-linked stress system prepares the body for fight-or-flight reactions, the oxytocin system is associated with calmness, social bonding, and emotional regulation. The research conducted at UNESP reinforces the idea that this circuit plays a fundamental role in modulating anxiety generated by chronic social stress in rats, an effect that has been little described in this species.
"Laboratory rats aren't as territorial as mice. Therefore, the study is unprecedented in demonstrating the effects of carbetocin in these animals, reinforcing its role in modulating anxiety," says Lucas Canto de Souza , who investigated the topic in his postdoctoral research supported by FAPESP and is currently a researcher in the Department of Bioengineering at the University of Texas in Dallas (United States).
Social defeat
In their study, the scientists employed a stress model in rodents known as "social defeat," wherein an intruder rat is placed in a cage with a resident male that lives with a lactating female and her newborn pups. This increases the residents' territoriality and aggressiveness, but the female and pups are removed from the cage during the interaction.
The intruder rat undergoes four sessions on different days with new residents and environments. Then, it is evaluated in an anxiety test called the elevated plus maze, a classic model for measuring anxiety-like behavior.
"Although stress didn't induce robust social avoidance, the rats exposed to defeat showed a significant reduction in exploration of the open arms of the maze. Since these arms are considered aversive environments, such behavior is interpreted as increased anxiety," says Souza.
The animals that were treated with carbetocin before the stress sessions maintained an exploratory pattern similar to that of the control group that did not experience stress. "The drug didn't make them more fearless, but rather acted preventively, mitigating the impact on anxiety-like behavior," says Souza.
To confirm whether this effect was associated with oxytocin receptors, the researchers conducted experiments with two oxytocin antagonists. "One of them completely blocked the protective action of carbetocin when administered beforehand, showing that the benefit depends directly on the activation of the oxytocinergic system," he says.
The researchers also analyzed the medial prefrontal cortex, a brain region involved in controlling responses to stress and anxiety. They observed that carbetocin increased the number of oxytocin receptors in subareas of this region, while the antagonists reduced this effect. This finding reinforces the role of this region in mediating the observed preventive effect.
"The study is further evidence of the relationship between oxytocin and this type of anxiety. However, despite the results, it's important to note that the study represents an initial step in biological understanding. For it to actually become a drug for this purpose, many more studies are needed before any responsible clinical application," he adds.
About São Paulo Research Foundation (FAPESP)
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe .
