The role of Fezolinetant in fear memory consolidation
Gallio Fronza, Mariana (Universitat Autònoma de Barcelona. Institut de Neurociències)
Torrent Bonilla, Marta (Universitat Autònoma de Barcelona. Institut de Neurociències)
Andero Galí, Raül (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Universitat Autònoma de Barcelona. Departament de Psicobiologia i de Metodologia de les Ciències de la Salut

Date:	2025
Abstract:	Modulation of fear memories has important implications for the treatment of different psychiatric disorders including fear-based disorders such as posttraumatic stress disorder (PTSD). The Tachykinin2 (Tac2)/Neurokinin B (NkB)/neurokinin 3 receptor (Nk3R) pathway is a potential candidate for treating fear-based disorders built on animal and human studies. Here we demonstrate that the Nk3R antagonist Fezolinetant presents sex-divergent effects in the processing of fear memories in mice exposed to cued-fear conditioning. Fezolinetant (1 and 10 mg/kg, intraperitoneally (i. p. )) administered 30 min after the fear acquisition impairs the fear memory consolidation in male mice, as measured by fear expression 24 h later, showing no effects in naturally cycling female mice, with no monitoring the estrous cycle. However, when the estrous cycle was monitored, Fezolinetant (1 and 10 mg/kg, i. p. ) enhanced fear memory consolidation during the proestrus phase, which suggests an effect dependent on high levels of the sex hormones estradiol and/or progesterone. Considering that Fezolinetant is currently a treatment for hot flashes in menopausal women, our results could be rapidly translated into clinical trials focused on treating or preventing fear-based disorders. Thus, these findings support the role of Tac2/NkB/Nk3R in fear memory consolidation and emphasize the importance of considering sex differences in the neurobiology of memory-related processes.
Grants:	Instituto de Salud Carlos III AC19/00077 Agencia Estatal de Investigación PID2020-112705RB-I00 Agencia Estatal de Investigación PID2023-146521OB-I00 Generalitat de Catalunya 2023/SGR-00152
Note:	Altres ajuts: acords transformatius de la UAB
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Cued-fear conditioning ; Memory processing ; Sex differences ; Proestrus
Published in:	Brain Research, Vol. 1865 (October 2025) , art. 149879, ISSN 1872-6240

DOI: 10.1016/j.brainres.2025.149879

6 p, 3.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles