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

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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
    Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA)

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.

Suggested Citation

  • Jackie Zhu & Elisa Hawkins & Kristin Phillips & Laxmikant S. Deshpande, 2020. "Assessment of Ketamine and its Enantiomers in an Organophosphate-Based Rat Model for Features of Gulf War Illness," IJERPH, MDPI, vol. 17(13), pages 1-16, June.
    • Handle: RePEc:gam:jijerp:v:17:y:2020:i:13:p:4710-:d:378438
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