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

Jackie Zhu, Elisa Hawkins, Kristin Phillips and Laxmikant S. Deshpande
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Jackie Zhu: Department of Biology, College of Humanities & Sciences, Virginia Commonwealth University, Richmond, VA 23298, USA
Elisa Hawkins: Departments of Neurology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
Kristin Phillips: School of Neuroscience, Virginia Tech, Blacksburg, VA 23298, USA
Laxmikant S. Deshpande: Departments of Neurology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA

IJERPH, 2020, vol. 17, issue 13, 1-16

Abstract: 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.

Keywords: organophosphates; DFP; depression; R -ketamine; S -ketamine; Sprague-Dawley rats (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2020
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