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4‐Hydroxytamoxifen attenuates methamphetamine‐induced nigrostriatal dopaminergic toxicity in intact and gonadetomized mice
Author(s) -
Kuo YuMin,
Chen HsiangHua,
Shieh ChihChang,
Chuang KuoPin,
Cherng Chianfang G.,
Yu Lung
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02089.x
Subject(s) - methamphetamine , dopaminergic , dopamine , chemistry , nigrostriatal pathway , medicine , striatum , superoxide , superoxide dismutase , endocrinology , pharmacology , biochemistry , antioxidant , substantia nigra , enzyme
The present study was undertaken to assess the ability of 4‐hydroxytamoxifen (4‐OHT) to alter methamphetamine‐induced nigrostriatal dopaminergic toxicity. Three daily doses of 4‐OHT (6 µg/day) effectively attenuated methamphetamine‐induced nigrostriatal dopamine depletions in both sexes of intact and gonadectomized C57BL/6 J mice. 4‐OHT alone did not alter the dopamine content levels in the striatum. Both male and female mice exhibited similar Cu, Zn‐superoxide dismutase protein levels in the striata whether after gonadectomy or 4‐OHT treatment. Furthermore, basal body temperature and methamphetamine‐induced hyperthermia were not affected by 4‐OHT treatment in either sex of mice. Using a lucigenen‐derived chemiluminescence assay, we found that 4‐OHT by itself can serve as a potent superoxide anion radical scavenger in vitro . The protective effects of 4‐OHT against methamphetamine‐induced nigrostriatal dopamine depletion can be, in part, due to its antioxidative characteristics. The free radical‐scavenging ability of 4‐OHT calls for further investigations for its uses in clinical practice.