Evaluation of the mood-stabilizing agent valproic acid as a preventative for toxoplasmosis in mice and activity against tissue cysts in mice

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dc.contributor.authorGoodwin, David G.en
dc.contributor.authorStrobl, J. S.en
dc.contributor.authorMitchell, S. M.en
dc.contributor.authorZajac, Anne M.en
dc.contributor.authorLindsay, David S.en
dc.date.accessed2014-06-16en
dc.date.accessioned2014-06-20T14:13:14Zen
dc.date.available2014-06-20T14:13:14Zen
dc.date.issued2008-04en
dc.description.abstractToxoplasma gondii is a common intracellular protozoan infection of humans worldwide. Severe disease can occur in immunocompromised individuals and the in the fetuses of nonimmune pregnant women. Chronic infection is associated with vision and hearing problems, and functional mental alterations, including schizophrenia. The mood-stabilizing agent valproic acid has been shown to inhibit the development of T. gondii in vitro at dosages that are normally achieved in the serum and cerebral spinal fluid of human patients and to have positive effects on the behavior of rats chronically infected with T. gondii. The present study was done to examine the in vivo activity of valproic acid against acute toxoplasmosis in mice. Two studies were done with valproic acid given in the drinking water at concentrations of 1.5 mg/ml (Experiment 1) or 3.0 mg/ml (Experiment 2). In a third experiment (Experiment 3), valproic acid was injected intraperitoneally (i.p.) at doses of 200 or 300 mg/kg every 12 hr. Valproic acid was not effective in preventing acute toxoplasmosis. All mice treated with valproic acid died or were killed and did not (P > 0.05) live significantly longer than the controls. Tachyzoites were demonstrated in the tissues of infected valproic-acid-treated mice. A fourth study was done to determine if valproic acid has activity against T. gondii tissue cysts in chronically infected mice. Mice were chronically infected with the ME-49 strain of T. gondii for 8 wk and then treated orally with valproic acid at approximately 6.6 mg/ml (800 mg/kg/day) in the drinking water for 10 wk (amount was varied due to increasing mouse weights). No significant differences (P > 0.05) were present in tissue cyst numbers in valproic-acid-treated T. gondii chronically infected mice and in mice chronically infected with T. gondii but not given valproic acid. Our results indicate that valproic acid, although effective in vitro against T. gondii tachyzoites, is not effective as a preventative in mice inoculated with T. gondii tachyzoites. Additionally, no activity against tissue cysts was observed in chronically T. gondii-infected valproic-acid-treated mice.en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationDavid G. Goodwin, Jeannine Strobl, Sheila M. Mitchell, Anne M. Zajac, and David S. Lindsay (2008). "Evaluation of the Mood-Stabilizing Agent Valproic Acid as a Preventative for Toxoplasmosis In Mice and Activity Against Tissue Cysts in Mice," Journal of Parasitology, Vol. 94, No. 2, pp. 555-557. doi: http://dx.doi.org/10.1645/GE-1331.1en
dc.identifier.doihttps://doi.org/10.1645/ge-1331.1en
dc.identifier.issn0022-3395en
dc.identifier.urihttp://hdl.handle.net/10919/49046en
dc.identifier.urlhttp://www.bioone.org/doi/abs/10.1645/GE-1331.1en
dc.language.isoenen
dc.publisherAmerican Society of Parasitologyen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subject1st-episode schizophreniaen
dc.subjectgondiien
dc.subjectinfectionen
dc.subjectantibodiesen
dc.subjectparasitesen
dc.subjectbehavioren
dc.subjectimpacten
dc.subjectrisken
dc.subjectratsen
dc.subjectparasitologyen
dc.titleEvaluation of the mood-stabilizing agent valproic acid as a preventative for toxoplasmosis in mice and activity against tissue cysts in miceen
dc.title.serialJournal of Parasitologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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