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
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.