TY - JOUR
T1 - Neurotoxic effects of methamphetamine
AU - Thrash, Bessy
AU - Karuppagounder, Senthilkumar S.
AU - Uthayathas, Subramaniam
AU - Suppiramaniam, Vishnu
AU - Dhanasekaran, Muralikrishnan
N1 - Funding Information:
Acknowledgments This study was supported by the Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL.
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
KW - Behavior
KW - Dopamine
KW - Methamphetamine
KW - Neurotoxicity
KW - Oxidative stress
KW - Parkinson's disease
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U2 - 10.1007/s11064-009-0042-5
DO - 10.1007/s11064-009-0042-5
M3 - Article
C2 - 19697126
AN - SCOPUS:76849098499
SN - 0364-3190
VL - 35
SP - 171
EP - 179
JO - Neurochemical Research
JF - Neurochemical Research
IS - 1
ER -