(2R,6R)-Hydroxynorketamine Treatment of Rats Exposed to Repetitive Low-Level Blast Injury.
(2R,6R)-Hydroxynorketamine Treatment of Rats Exposed to Repetitive Low-Level Blast Injury.
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DOI：
10.1089/neur.2022.0088
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发表时间：
2023
影响因子：
2.4
通讯作者：
Elder, Gregory A. A.
中科院分区：
文献类型：
--
作者：
Garcia, Georgina Perez;Perez, Gissel M. M.;De Gasperi, Rita;Sosa, Miguel A. Gama;Otero-Pagan, Alena;Abutarboush, Rania;Kawoos, Usmah;Statz, Jonathan K. K.;Patterson, Jacob;Zhu, Carolyn W. W.;Hof, Patrick R. R.;Cook, David G. G.;Ahlers, Stephen T. T.;Elder, Gregory A. A.
Many military veterans who experienced blast-related traumatic brain injuries (TBIs) in the conflicts in Iraq and Afghanistan suffer from chronic cognitive and mental health problems, including post-traumatic stress disorder (PTSD). Male rats subjected to repetitive low-level blast exposure develop chronic cognitive and PTSD-related traits that develop in a delayed manner. Ketamine has received attention as a treatment for refractory depression and PTSD. (2R,6R)-hydroxynorketamine [(2R,6R)-HNK] is a ketamine metabolite that exerts rapid antidepressant actions. (2R,6R)-HNK has become of clinical interest because of its favorable side-effect profile, low abuse potential, and oral route of administration. We treated three cohorts of blast-exposed rats with (2R,6R)-HNK, beginning 7–11 months after blast exposure, a time when the behavioral phenotype is established. Each cohort consisted of groups (n = 10–13/group) as follows: 1) Sham-exposed treated with saline, 2) blast-exposed treated with saline, and 3) blast-exposed treated with a single dose of 20 mg/kg of (2R,6R)-HNK. (2R,6R)-HNK rescued blast-induced deficits in novel object recognition (NOR) and anxiety-related features in the elevated zero maze (EZM) in all three cohorts. Exaggerated acoustic startle was reversed in cohort 1, but not in cohort 3. (2R,6R)-HNK effects were still present in the EZM 12 days after administration in cohort 1 and 27 days after administration in NOR testing of cohorts 2 and 3. (2R,6R)-HNK may be beneficial for the neurobehavioral syndromes that follow blast exposure in military veterans. Additional studies will be needed to determine whether higher doses or more extended treatment regimens may be more effective.
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影响因子：
3.6
作者：
Aleksandrova, Lily R.;Wang, Yu Tian;Phillips, Anthony G.
通讯作者：
Phillips, Anthony G.
DOI：
10.1016/j.pbb.2020.172973
发表时间：
2020-09
期刊：
Pharmacology, biochemistry, and behavior
影响因子：
--
作者：
Elmer GI;Tapocik JD;Mayo CL;Zanos P;Gould TD
通讯作者：
Gould TD
影响因子：
3.4
作者：
Ahlers ST;Vasserman-Stokes E;Shaughness MC;Hall AA;Shear DA;Chavko M;McCarron RM;Stone JR
通讯作者：
Stone JR
影响因子：
3
作者：
GREENHOUSE, SW;GEISSER, S
通讯作者：
GEISSER, S
影响因子：
2.5
作者：
Elder, Gregory A.;Ehrlich, Michelle E.;Gandy, Sam
通讯作者：
Gandy, Sam