A new peer review research report is published in Brain Medicine Revealing a single dose of penetration agent taken shortly after the trauma event, severely inhibiting fear expression in female mice. These findings provide strong preclinical support for the use of NK3R antagonism as a gender-specific, time-sensitive intervention to reduce the risk of post-traumatic stress disorder (PTSD).
Targeting the roots of fear memory
Fear memory is a core feature of PTSD, especially when neutral cues are emotional after post-traumatic. From School of Neuroscience, University of Barcelona Explore how fear consolidation uses osanetant, a selective blocker of neuroprotein 3 receptor (NK3R), shortly after exposure to stress, as part of the pathway in which speedoster 2 (TAC2) involves affective regulation.
In the study, female mice suffered fixed stress (verified PTSD-like model) and then a single injection of osanetant was given after 30 minutes. Six days later, animals were trained and tested using standard fear conditioning protocols. Compared with the control group, the freezing behavior of osanetant was significantly reduced (p = 0.038), indicating impaired consolidation of fear memory.
“This is a particularly important window,” said Neha Acharya and Jaime Fabregat, co-first authors of this article. “We are not stopping fear learning, but reducing the extent to which it is biologically stored.”
Why focus on female rats?
The study zeroes gender as a biological variable, a key but historically underrepresented factor in neuroscience. PTSD is twice as common in women, but most rodent models remain male-dominated. The team aims to address this imbalance directly.
“We have known for years that women and men’s brains have not handled trauma in the same way,” said Dr. Raül Andero, a professor of research and senior author and principal investigator at ICREA. “However, female-centric pharmacological strategies are still rare. This study takes the first step towards closing the gap.”
Context: Stress can reverse the effect of the drug
Strangely, early work in the same lab showed that osanet actually increased fear expression in stress-free female mice, which is seen here. The authors suspect that stress exposure rewires neural circuits and potentially attract different plasticity mechanisms. Factors such as β-catenin, BDNF, GSK-3β and MTOR are all candidates mediating this switch.
Will trauma “vegetarian” the brain respond differently to drugs? Does NK3R antagonism work only when it exceeds the stress threshold? How will these findings translate into acute treatments in humans, such as post-aggression or post-event interventions?
“These are pressing questions,” Dr. Andro said. “Especially because it has been proven to be safe in clinical trials.”
Going towards fast translation
The study was not without limitations: only female mice were tested, no estrus cycle was followed, and no molecular markers were analyzed. Nevertheless, the behavioral results are robust – the pharmacological window is both narrow and operational.
Given the safety of Osanet, the researchers believe that future research could explore its use in an emergency room environment, providing a rapidly responding pharmacological shield to prevent trauma-induced memory over-curing.
Peer-reviewed Brevia article “NK3R antagonism reduces fear expression in PTSD model in female mice” appeared online on April 8, 2025 Brain Medicine (Genome Press), and can be accessed freely
about Brain Medicine: Brain Medicine (ISSN: 2997-2639) is a peer-reviewed medical research journal published by the New York Genome Press. Brain Medicine It is a new home for interdisciplinary pathways from innovation in basic neuroscience to brain medicine transformation programs. The journal’s scope includes all clinical disciplines and their interfaces to the basic science, causes, outcomes, treatments and social impacts of brain diseases.
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