Nk3R antagonism decreases concern reminiscence consolidation. (A) Experimental process of concern reminiscence consolidation after stress. Created with Biorender. (B) Concern acquisition and expression in mice administered with Osanetant. (C) Impact within the concern reminiscence consolidation after administration of Osanetant (5 mg/kg, ip) or Automobile 30 min after stress (IMO) in grownup females (n = 12 per group) (p = 0.038, η2 = 0.798). Analyzed by Generalized Linear Mannequin with least important distinction (LSD) correction. Credit score: Raül Andero
A brand new report printed in Mind Medication reveals {that a} single dose of the drug Osanetant, administered shortly after a traumatic occasion, considerably dampens concern expression in feminine mice. The findings present robust preclinical help for utilizing Nk3R antagonism as a sex-specific, time-sensitive intervention to scale back the chance of posttraumatic stress dysfunction (PTSD).
Concern reminiscence is a core characteristic of PTSD, particularly when impartial cues grow to be emotionally loaded after trauma. The analysis workforce from the Institut de Neurociències of the Universitat Autònoma de Barcelona explored how concern consolidation may very well be interrupted shortly after publicity to emphasize, utilizing Osanetant—a selective blocker of the neurokinin 3 receptor (Nk3R), which is a part of the Tachykinin 2 (Tac2) pathway concerned in emotional regulation.
Within the research, feminine mice underwent immobilization stress (a validated PTSD-like mannequin), adopted by a single injection of Osanetant half-hour later. Six days afterward, the animals had been educated and examined utilizing normal concern conditioning protocols. People who obtained Osanetant confirmed considerably decrease freezing habits in comparison with controls (p = 0.038), indicating impaired consolidation of concern reminiscence.
“This is an especially important window,” mentioned 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 deal with feminine mice?
The research zeroes in on intercourse as a organic variable, a important however traditionally underrepresented think about neuroscience. PTSD is twice as prevalent in ladies, but most rodent fashions are nonetheless male-dominated. The workforce aimed to instantly deal with this imbalance.
“We’ve known for years that female and male brains don’t process trauma the same way,” mentioned Dr. Raül Andero, who’s an ICREA Analysis Professor and, senior creator and principal investigator. “Yet female-focused pharmacological strategies remain rare. This study takes a first step toward closing that gap.”
Context issues: Stress flips the drug’s impact
Curiously, earlier work from the identical lab confirmed that Osanetant truly elevated concern expression in non-stressed feminine mice—reverse to what was seen right here. The authors suspect that stress publicity rewires neural circuits, probably participating totally different plasticity mechanisms. Elements like β-catenin, BDNF, GSK-3β, and mTOR are all candidates for mediating this change.
Might trauma ‘prime’ the mind to reply in another way to medicine? Does Nk3R antagonism solely work when stress thresholds are crossed? And the way may these findings translate to acute therapy in people, comparable to post-assault or post-accident interventions?
“These are urgent questions,” mentioned Dr. Andero. “Especially since Osanetant is already proven safe in clinical trials.”
The research will not be with out limitations: solely feminine mice had been examined, estrous cycles weren’t tracked, and no molecular markers had been analyzed. Nonetheless, the behavioral consequence is strong—and the pharmacological window is each slender and actionable.
Given Osanetant’s security profile, the researchers counsel future research may discover its use in emergency room settings, providing a rapid-response pharmacological protect in opposition to trauma-induced reminiscence overconsolidation.
Extra info:
NK3R antagonism reduces concern expression in a PTSD-like mannequin of feminine mice, Mind Medication (2025). DOI: 10.61373/bm025l.0035
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Put up-trauma drug blocks concern response in feminine mice, research reveals (2025, April 8)
retrieved 8 April 2025
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