Submit-trauma drug blocks worry response in feminine mice, research exhibits

A brand new report printed in Mind Drugs reveals {that a} single dose of the drug Osanetant, administered shortly after a traumatic occasion, considerably dampens worry expression in feminine mice. The findings present sturdy preclinical help for utilizing Nk3R antagonism as a sex-specific, time-sensitive intervention to scale back the danger of posttraumatic stress dysfunction (PTSD).

Concern reminiscence is a core function of PTSD, particularly when impartial cues turn out to be emotionally loaded after trauma. The analysis group from the Institut de Neurociències of the Universitat Autònoma de Barcelona explored how worry consolidation might be interrupted shortly after publicity to stress, 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 have been educated and examined utilizing customary worry conditioning protocols. Those who obtained Osanetant confirmed considerably decrease freezing conduct in comparison with controls (p = 0.038), indicating impaired consolidation of worry reminiscence.

“That is an particularly necessary window,” mentioned Neha Acharya and Jaime Fabregat, co-first authors of the paper. “We’re not stopping worry studying—however lowering how intensely it will get biologically saved.”

Why deal with feminine mice?

The research zeroes in on intercourse as a organic variable, a essential however traditionally underrepresented think about neuroscience. PTSD is twice as prevalent in ladies, but most rodent fashions are nonetheless male-dominated. The group aimed to instantly tackle this imbalance.

“We have recognized for years that feminine and male brains do not course of trauma the identical manner,” mentioned Dr. Raül Andero, who’s an ICREA Analysis Professor and, senior creator and principal investigator. “But female-focused pharmacological methods stay uncommon. This research takes a primary step towards closing that hole.”

Context issues: Stress flips the drug’s impact

Curiously, earlier work from the identical lab confirmed that Osanetant really elevated worry expression in non-stressed feminine mice—reverse to what was seen right here. The authors suspect that stress publicity rewires neural circuits, probably partaking completely different plasticity mechanisms. Components like β-catenin, BDNF, GSK-3β, and mTOR are all candidates for mediating this change.

May trauma ‘prime’ the mind to reply otherwise to medication? Does Nk3R antagonism solely work when stress thresholds are crossed? And the way may these findings translate to acute remedy in people, corresponding to post-assault or post-accident interventions?

“These are pressing questions,” mentioned Dr. Andero. “Particularly since Osanetant is already confirmed protected in medical trials.”

The research just isn’t with out limitations: solely feminine mice have been examined, estrous cycles weren’t tracked, and no molecular markers have been analyzed. Nonetheless, the behavioral consequence is strong—and the pharmacological window is each slim 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 defend towards trauma-induced reminiscence overconsolidation.

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Genomic Press