According to a study led by the Institut de Neurociències of the UAB, Osanetant decreases the intensity with which the memory of fear is consolidated, thus preventing the onset of post-traumatic stress disorder (PTSD). The study, conducted with female mice, highlights substancial sex-specific differences when it comes to fear response.
After a traumatic experience, apparently neutral stimuli can be charged with a negative connotation, which can trigger PTSD. To prevent this, a team from the Institut de Neurociències of the Universitat Autònoma de Barcelona (INc-UAB) has explored the possibility of interrupting the consolidation of trauma memory by intervening shortly after exposure to stress.
In the study, female mice were subjected to immobilisation stress (a validated model similar to PTSD), followed by a single dose of Osanetant at 30 minutes. Six days later, standard fear conditioning and extinction protocols were applied. The results show that the animals that received Osanetant had a significantly lower freezing response (fear index), indicating that the fear memory had not been consolidated with the same intensity.
"It is not a matter of preventing the learning of fear, but of reducing the intensity with which it is biologically registered," explains Neha Acharya. "It is crucial however to administer the drug right after the negative experience, since the time window is particularly relevant," adds Jaime Fabregat. Both are predoctoral researchers at INc-UAB and co-first authors of the article, published in the journal Brain Medicine.
Interestingly, previous studies conducted in the same laboratory had shown that Osanetant increased the fear response in female mice, rather than reducing it. However, those studies were performed in models without prior exposure to trauma. The opposite effect observed in the current study could be explained by the fact that exposure to trauma would have reconfigured the neural circuits, activating different plasticity mechanisms.
Maybe the trauma "prepares" the brain to respond differently to the drug? Will the drug only work once a stress threshold has been passed? And how could these results be transferred to human contexts, as for example in immediate interventions after an aggression or accident?
"These are urgent questions," says Raül Andero, coordinator of the study and ICREA research professor at INc-UAB. "Particularly when taking into account that Osanetant has already proven to be safe in clinical trials."
The study highlights sex as a crucial but often overlooked biological variable in neuroscience. PTSD is twice as common in females as in males, yet most rodent models are still based on male individuals. The team wanted to break this trend.
Although the study had some limitations - only female mice were used, hormonal cycles were not controlled, and molecular markers were not analysed - the behavioural results are solid and the window for pharmacological intervention is brief, but very promising.
Given the demonstrated safety of Osanetant, researchers suggest that future studies could explore its use in emergency services as a fast-acting pharmacological measure to prevent overconsolidation of traumatic memories.
