title: Effects of vitamin E supplementation on plasma membrane permeabilization and fluidization induced by chlorpromazine in the rat brain.
abstract: Neurotransmitter receptors play a key role in most research on antipsychotic drugs, but little is known about the effects of these drugs on the plasma membrane in the central nervous system. Therefore, we investigated whether chlorpromazine (CPZ), a typical phenothiazine antipsychotic drug, affects the plasma membrane integrity in the rat brain, and if so, whether these membrane alterations can be prevented by dietary supplementation with vitamin E, which has been shown to be an antioxidant and also a membrane-stabilizer. Leakage of [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG)-6-phosphate from rat striatal slices and decrease in 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy were used as indexes for plasma membrane permeabilization and fluidization, respectively. CPZ induced leakage of [(18)F]FDG-6-phosphate from striatal slices, and the leakage was delayed in the vitamin E-supplemented group compared to that in the normal diet group. The decrease in plasma membrane anisotropy induced by CPZ was significantly attenuated by vitamin E supplementation. Chronic treatment with alpha-phenyl-N-tert-butyl nitrone, a free radical scavenger, had no effect on CPZ-induced plasma membrane permeabilization, and the treatment with CPZ did not induce lipid peroxidation. CPZ can reduce plasma membrane integrity in the brain, and this reduction can be prevented by vitamin E via its membrane-stabilizing properties, not via its antioxidant activity.
authors.affiliation: Department of Neuropsychiatry, University of Fukui, Fukui, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Maruoka
authors.forename: Tetsuhito
authors.initials: T
authors.lastname: Murata
authors.forename: Naoto
authors.initials: N
authors.lastname: Omata
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takashima
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fujibayashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Wada
mesh_terms: D000818:Animals; D016880:Anisotropy; D000975:Antioxidants / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000633:toxicity*; D001345:Autoradiography; D001921:Brain / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002746:Chlorpromazine / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D024505:Tocopherols; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D014150:Antipsychotic Agents; D019788:Fluorodeoxyglucose F18; C047515:2-fluoro-2-deoxyglucose-6-phosphate; D019298:Glucose-6-Phosphate; D024502:alpha-Tocopherol; D024505:Tocopherols; D002746:Chlorpromazine