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Open AccessArticle

Assessment of Ketamine and its Enantiomers in an Organophosphate-Based Rat Model for Features of Gulf War Illness

1
Department of Biology, College of Humanities & Sciences, Virginia Commonwealth University, Richmond, VA 23298, USA
2
Departments of Neurology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
3
School of Neuroscience, Virginia Tech, Blacksburg, VA 23298, USA
4
Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2020, 17(13), 4710; https://doi.org/10.3390/ijerph17134710
Received: 1 June 2020 / Revised: 19 June 2020 / Accepted: 29 June 2020 / Published: 30 June 2020
(This article belongs to the Special Issue Gulf War Illness, A Drug and Environmentally-TriggeredCondition)
Approximately 33% of U.S. soldiers from the first Gulf War suffer from a multi-system disorder known as the Gulf War Illness (GWI). GW veterans suffer from a cluster of symptoms that prominently include fatigue and can include mood-related symptoms. Compared to traditional antidepressants, ketamine (KET) produces a fast-onset and long-lasting antidepressant response, but assessments of KET for GWI-related depression are lacking. The etiology of GWI is multi-factorial and exposure to organophosphates (OP) during deployment is one of the factors underlying GWI development. Here, male Sprague-Dawley rats were repeatedly exposed to an OP DFP and three months later these rats, when assessed on a battery of rodent behavioral assays, displayed signs consistent with aspects of GWI characteristics. When treated with a sub-anesthetic dose of KET (3, 5, or 10 mg/kg, i.p.), DFP-treated rats exhibited a significant improvement in immobility time, open-arm exploration, and sucrose consumption as early as 1 h and much of these effects persisted at 24-h post-KET injection. KET’s stereoisomers, R-KET and S-KET, also exhibited such effects in DFP rats, with R-KET being the more potent isomer. Our studies provide a starting point for further assessment of KET for GWI depression. View Full-Text
Keywords: organophosphates; DFP; depression; R-ketamine; S-ketamine; Sprague-Dawley rats organophosphates; DFP; depression; R-ketamine; S-ketamine; Sprague-Dawley rats
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Zhu, J.; Hawkins, E.; Phillips, K.; Deshpande, L.S. Assessment of Ketamine and its Enantiomers in an Organophosphate-Based Rat Model for Features of Gulf War Illness. Int. J. Environ. Res. Public Health 2020, 17, 4710.

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