BARCELONA, Catalonia, Spain, 8 April 2025 – A new Brevia (peer-reviewed research report) published in Brain Medicine reveals that a single dose of the drug Osanetant, administered shortly after a traumatic event, significantly dampens fear expression in female mice. The findings provide strong preclinical support for using Nk3R antagonism as a sex-specific, time-sensitive intervention to reduce the risk of posttraumatic stress disorder (PTSD).
Targeting fear memory at its roots
Fear memory is a core feature of PTSD, especially when neutral cues become emotionally loaded after trauma. The research team from the Institut de Neurociències of the Universitat Autònoma de Barcelona explored how fear consolidation could be interrupted shortly after exposure to stress, using Osanetant—a selective blocker of the neurokinin 3 receptor (Nk3R), which is part of the Tachykinin 2 (Tac2) pathway involved in emotional regulation.
In the study, female mice underwent immobilization stress (a validated PTSD-like model), followed by a single injection of Osanetant 30 minutes later. Six days afterward, the animals were trained and tested using standard fear conditioning protocols. Those that received Osanetant showed significantly lower freezing behavior compared to controls (p = 0.038), indicating impaired consolidation of fear memory.
"This is an especially important window," said Neha Acharya and Jaime Fabregat, co-first authors of the paper. "We're not preventing fear learning—but reducing how intensely it gets biologically stored."
Why focus on female mice?
The study zeroes in on sex as a biological variable, a critical but historically underrepresented factor in neuroscience. PTSD is twice as prevalent in women, yet most rodent models are still male-dominated. The team aimed to directly address this imbalance.
"We've known for years that female and male brains don't process trauma the same way," said Dr. Raül Andero who is an ICREA Research Professor and, senior author and principal investigator. "Yet female-focused pharmacological strategies remain rare. This study takes a first step toward closing that gap."
Context matters: stress flips the drug's effect
