Post-trauma drug blocks fear response in female mice, study shows

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

Curiously, earlier work from the same lab showed that Osanetant actually increased fear expression in non-stressed female mice—opposite to what was seen here. The authors suspect that stress exposure rewires neural circuits, potentially engaging different plasticity mechanisms. Factors like β-catenin, BDNF, GSK-3β, and mTOR are all candidates for mediating this switch.

Could trauma ‘prime’ the brain to respond differently to drugs? Does Nk3R antagonism only work when stress thresholds are crossed? And how might these findings translate to acute treatment in humans, such as post-assault or post-accident interventions?

“These are urgent questions,” said Dr. Andero. “Especially since Osanetant is already proven safe in clinical trials.”

Toward fast-track translation

The study is not without limitations: only female mice were tested, estrous cycles weren’t tracked, and no molecular markers were analyzed. Still, the behavioral outcome is robust—and the pharmacological window is both narrow and actionable.

Given Osanetant’s safety profile, the researchers suggest future studies could explore its use in emergency room settings, offering a rapid-response pharmacological shield against trauma-induced memory overconsolidation.

The peer-reviewed Brevia Article “NK3R antagonism reduces fear expression in a PTSD-like model of female mice” appears online on 8 April 2025 in Brain Medicine (Genomic Press) and is freely accessible at https://doi.org/10.61373/bm025l.0035.

About Brain Medicine: Brain Medicine (ISSN: 2997-2639) is a peer-reviewed medical research journal published by Genomic Press, New York. Brain Medicine is a new home for the cross-disciplinary pathway from innovation in fundamental neuroscience to translational initiatives in brain medicine. The journal’s scope includes the underlying science, causes, outcomes, treatments, and societal impact of brain disorders across all clinical disciplines and their interface.