TY - JOUR
T1 - PTSD-related behavioral traits in a rat model of blast-induced mtbi are reversed by the MGLUR2/3 receptor antagonist bci-838
AU - Perez-Garcia, Georgina
AU - de Gasperi, Rita
AU - Gama Sosa, Miguel A.
AU - Perez, Gissel M.
AU - Otero-Pagan, Alena
AU - Tschiffely, Anna
AU - McCarron, Richard M.
AU - Ahlers, Stephen T.
AU - Elder, Gregory A.
AU - Gandy, Sam
N1 - Publisher Copyright:
© 2018 Perez-Garcia et al.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Battlefield blast exposure related to improvised explosive devices (IEDs) has become the most common cause of traumatic brain injury (TBI) in the recent conflicts in Iraq and Afghanistan. Mental health problems are common after TBI. A striking feature in the most recent veterans has been the frequency with which mild TBI (mTBI) and posttraumatic stress disorder (PTSD) have appeared together, in contrast to the classical situations in which the presence of mTBI has excluded the diagnosis of PTSD. However, treatment of PTSD-related symptoms that follow blast injury has become a significant problem. BCI-838 (MGS0210) is a Group II metabotropic glutamate receptor (mGluR2/3) antagonist prodrug, and its active metabolite BCI-632 (MGS0039) has proneurogenic, procognitive, and antidepressant activities in animal models. In humans, BCI-838 is currently in clinical trials for refractory depression and suicidality. The aim of the current study was to determine whether BCI-838 could modify the anxiety response and reverse PTSD-related behaviors in rats exposed to a series of low-level blast exposures designed to mimic a human mTBI or subclinical blast exposure. BCI-838 treatment reversed PTSDrelated behavioral traits improving anxiety and fear-related behaviors as well as long-term recognition memory. Treatment with BCI-838 also increased neurogenesis in the dentate gyrus (DG) of blast-exposed rats. The safety profile of BCI-838 together with the therapeutic activities reported here, make BCI-838 a promising drug for the treatment of former battlefield Warfighters suffering from PTSD-related symptoms following blast-induced mTBI.
AB - Battlefield blast exposure related to improvised explosive devices (IEDs) has become the most common cause of traumatic brain injury (TBI) in the recent conflicts in Iraq and Afghanistan. Mental health problems are common after TBI. A striking feature in the most recent veterans has been the frequency with which mild TBI (mTBI) and posttraumatic stress disorder (PTSD) have appeared together, in contrast to the classical situations in which the presence of mTBI has excluded the diagnosis of PTSD. However, treatment of PTSD-related symptoms that follow blast injury has become a significant problem. BCI-838 (MGS0210) is a Group II metabotropic glutamate receptor (mGluR2/3) antagonist prodrug, and its active metabolite BCI-632 (MGS0039) has proneurogenic, procognitive, and antidepressant activities in animal models. In humans, BCI-838 is currently in clinical trials for refractory depression and suicidality. The aim of the current study was to determine whether BCI-838 could modify the anxiety response and reverse PTSD-related behaviors in rats exposed to a series of low-level blast exposures designed to mimic a human mTBI or subclinical blast exposure. BCI-838 treatment reversed PTSDrelated behavioral traits improving anxiety and fear-related behaviors as well as long-term recognition memory. Treatment with BCI-838 also increased neurogenesis in the dentate gyrus (DG) of blast-exposed rats. The safety profile of BCI-838 together with the therapeutic activities reported here, make BCI-838 a promising drug for the treatment of former battlefield Warfighters suffering from PTSD-related symptoms following blast-induced mTBI.
KW - BCI-838
KW - Blast
KW - MGluR2/3
KW - Metabotropic glutamate receptor
KW - Posttraumatic stress disorder
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=85042092246&partnerID=8YFLogxK
U2 - 10.1523/ENEURO.0357-17.2018
DO - 10.1523/ENEURO.0357-17.2018
M3 - Article
C2 - 29387781
AN - SCOPUS:85042092246
SN - 2373-2822
VL - 5
JO - eNeuro
JF - eNeuro
IS - 1
M1 - e0357-17.2018
ER -