ATTENUATION OF METHAMPHETAMINE-INDUCED NEUROTOXICITY IN COPPER ZINC SUPEROXIDE-DISMUTASE TRANSGENIC MICE/

Citation
Jl. Cadet et al., ATTENUATION OF METHAMPHETAMINE-INDUCED NEUROTOXICITY IN COPPER ZINC SUPEROXIDE-DISMUTASE TRANSGENIC MICE/, Journal of neurochemistry, 62(1), 1994, pp. 380-383
Citations number
24
Categorie Soggetti
Biology,Neurosciences
Journal title
ISSN journal
00223042
Volume
62
Issue
1
Year of publication
1994
Pages
380 - 383
Database
ISI
SICI code
0022-3042(1994)62:1<380:AOMNIC>2.0.ZU;2-6
Abstract
Administration of methamphetamine (METH) to rats and nonhuman primates causes loss of terminals in the nigrostriatal dopaminergic system. Th e mechanism by which METH causes its neurotoxicity is not known. To ev aluate further the role of oxyradicals in METH-induced neurotoxicity, we have tested its effects in CuZn superoxide dismutase (SOD) transgen ic (Tg) mice, which express the human CuZnSOD gene. In non-Tg mice, ac ute METH administration causes significant decreases in levels of dopa mine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striata an d cortices of non-Tg mice. In contrast, there were no significant decr eases in cortical or striatal DA in the SOD-Tg mice. The effects of ME TH on DOPAC were also attenuated in both structures of these SOD-Tg mi ce. Chronic METH administration caused decreases in levels of striatal DA and DOPAC in the non-Tg mice, whereas the SOD-Tg mice were not aff ected. These results suggest that METH-induced dopaminergic toxicity i n mice may be secondary to increased production of reactive oxygen spe cies such as the superoxide radical.