ORIGINAL RESEARCH article
Front. Neurol.
Sec. Neurotrauma
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1594335
Serotonin 5-HT2A receptor expression is chronically decreased in the anterior cerebral cortex of male rats following repetitive low-level blast exposure
Provisionally accepted
Rita De Gasperi1
Georgina Perez Garcia1
Miguel A Gama Sosa1
Gissel M Perez1Rania Abutarboush2Usmah Kawoos2
Patrick R Hof3
CAROLYN ZHU1,3Stephen T Ahlers2
Gregory Elder3,4*- 1James J. Peters VA Medical Center, United States Department of Veterans Affairs, Bronx, New York, United States
- 2Naval Medical Research Center, Silver Spring, Maryland, United States
- 3Icahn School of Medicine at Mount Sinai, New York, New York, United States
- 4Department of Neurology, James J. Peters VA Medical Center, New York, United States
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Introduction: Many Veterans who experienced blast-related traumatic brain injuries (TBIs) in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems that include depression and post-traumatic stress disorder (PTSD). Male rats exposed to repetitive lowlevel blast develop chronic cognitive and PTSD-related behavioral traits that are present for more than one year after exposure. Psychedelic agents alter cognition as well as mood and agents such as psilocybin have gained attention as possible treatments for the mental health disorders that affect Veterans. The best-known action of psilocybin's metabolite psilocin is to stimulate the serotonin 2A receptor (5-HT2AR). The aim of this study was to determine whether 5-HT2AR levels are altered by blast exposure.Methods: 5-HT2AR expression was examined by Western blot in 7 cohorts of rats exposed to low level repetitive blast collected from 2 weeks to 12 months after blast exposure. The analysis included three brain regions (anterior cerebral cortex, hippocampus and amygdala) that were chosen based on being relevant to fear learning and the biological basis of PTSD. Possible correlations between Western blot data and behavioral outcomes were evaluated.Results: 5-HT2AR was chronically decreased in anterior cortex of blast-exposed rats in all cohorts except the one studied at two weeks after blast exposure. 5-HT2AR levels were variably affected in the other regions. 5-HT2AR expression correlated differently in blast and control rats in some behavioral parameters.Conclusions: These findings have implications for understanding the neurochemical basis of blast-induced cognitive and behavioral changes. They also suggest 5-HT2AR as a potential therapeutic target for treatment of PTSD-related symptoms that follow blast injury.
Keywords: blast, serotonin 5-HT2A receptor, male rats, Military veterans, Traumatic Brain Injury
Received: 15 Mar 2025; Accepted: 03 Jun 2025.
Copyright: © 2025 De Gasperi, Perez Garcia, Gama Sosa, Perez, Abutarboush, Kawoos, Hof, ZHU, Ahlers and Elder. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Gregory Elder, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, United States
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