Deprenyl? Meth. & Neurotoxicity 4/95 Study

[Concerned Citizen]

Record from database: MEDLINE

Title
Methamphetamine-induced serotonin neurotoxicity is mediated by
superoxide radicals.
Author
Hirata H, Ladenheim B, Rothman RB, Epstein C, Cadet JL
Address
Molecular Neuropsychiatry Section, NIH/NIDA, Baltimore, MD
21224, USA.
Source
Brain Res, 677: 2, 1995 Apr 24, 345-7

Abstract
Methamphetamine (METH) causes deleterious effects in brain
monoaminergic systems. Evidence has accumulated to suggest that these
effects may be
mediated via the overproduction of the superoxide radicals. We
have recently shown that METH-induced dopamine (DA) depletion is
attenuated in
copper-zinc superoxide dismutase (CuZnSOD) transgenic (Tg) mice.
In the present study, we have used receptor autoradiographic studies of
[125I]RTI-55
labeled serotonin (5-HT) uptake sites to evaluate the effect of
a two dosing schedule (5 mg/kg or 10 mg/kg x 4) of METH on striatal 5-
HT uptake sites in
nontransgenic (Non-Tg), heterozygous (Hetero) and homozygous
(Homo) SOD-Tg mice. The low dose caused no significant changes in
striatal 5-HT
uptake sites in any of the groups. The high dose caused marked
decreases (-74%) in striatal 5-HT uptake sites in Non-Tg mice. In
contrast, 5-HT uptake
sites showed only a 31% decrease in homozygous SOD-Tg mice
whereas heterozygous SOD-Tg mice showed 63% depletion. These results
show that
increased SOD activity can protect against METH-induced
neurotoxicity in striatal serotonergic terminals. These data provide
further evidence for a role of
oxidative stress in the neurotoxic effects of METH.