Neurotoxic effects of methamphetamine.
In Parkinson's disease, depletion of dopamine in the striatum leads to various symptoms such as tremor, rigidity and akinesia. Methamphetamine use has significantly increased in USA and around the world and there are several reports showing that its long-term use increases the risk for dopamine depletion. However, the toxic mechanisms of methamphetamine are not well understood. This study was undertaken to gain greater mechanistic understanding of the toxicity induced by methamphetamine. We evaluated the effect of methamphetamine on the generation of reactive oxygen species, mitochondrial monoamine oxidase, complex I & IV activities. Behavioral analysis evaluated the effect on catalepsy, akinesia and swim score. Neurotransmitter levels were evaluated using high pressure liquid chromatography (HPLC) electrochemical detection (ECD). Results showed that methamphetamine caused significant generation of reactive oxygen species and decreased complex I activity in the mitochondria leading to dopamine depletion in the striatum.
Thrash
Bessy
B
Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, 4306 Walker building, Auburn, AL 36849, USA.
Karuppagounder
Senthilkumar S
SS
Uthayathas
Subramaniam
S
Suppiramaniam
Vishnu
V
Dhanasekaran
Muralikrishnan
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D004563:Electrochemistry; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology
D017382:Reactive Oxygen Species; D008694:Methamphetamine; D008995:Monoamine Oxidase
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