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Effects of vitamin E supplementation on plasma membrane permeabilization and fluidization induced by chlorpromazine in the rat brain

Department of Neuropsychiatry, University of Fukui, Fukui, Japan

^* To whom correspondence should be addressed.

	Abstract

Neurotransmitter receptors play a key role in most research on antipsychoticdrugs, but little is known about the effects of these drugs on the plasmamembrane in the central nervous system. Therefore, we investigatedwhether chlorpromazine (CPZ), a typical phenothiazine antipsychotic drug,affects the plasma membrane integrity in the rat brain, and if so, whetherthese membrane alterations can be prevented by dietary supplementationwith vitamin E, which has been shown to be an antioxidant and alsoa membrane-stabilizer. Leakage of [18F]2-fluoro-2-deoxy-D-glucose([18F]FDG)-6-phosphate from rat striatal slices and decrease in1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy were used as indexesfor plasma membrane permeabilization and fluidization, respectively. CPZinduced leakage of [18F]FDG-6-phosphate from striatal slices, and theleakage was delayed in the vitamin E-supplemented group comparedto that in the normal diet group. The decrease in plasma membraneanisotropy induced by CPZ was significantly attenuated by vitamin Esupplementation. Chronic treatment with _-phenyl-N-tert-butyl nitrone,a free radical scavenger, had no effect on CPZ-induced plasma membranepermeabilization, and the treatment with CPZ did not induce lipidperoxidation. CPZ can reduce plasma membrane integrity in the brain, andthis reduction can be prevented by vitamin E via its membrane-stabilizingproperties, not via its antioxidant activity.

Key Words: membrane permeability, membrane fluidity, chlorpromazine, vitamin E, striatal slices, extrapyramidal side effects

First published on January 21, 2008, doi:10.1177/0269881107078487

Journal of Psychopharmacology 2008;22:119.

A more recent version of this article appeared on March 1, 2008


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