Attenuation of cocaine and methamphetamine neurotoxicity by coenzyme Q10.
The neurotoxic effects of cocaine and methamphetamine (METH) were studied in mice brain with a primary objective to determine the neuroprotective potential of coenzyme Q10 (CoQ10) in drug addiction. Repeated treatment of cocaine or METH induced significant reduction in the striatal dopamine and CoQ10 in mice. Cocaine or METH-treated mice exhibited increased thiobarbituric acid reactive substances (TBARs) in the striatum and cerebral cortex without any significant change in the cerebellum. Complex I immunoreactivity was inhibited in both cocaine and METH-treated mice, whereas tyrosine hydroxylase (TH) immunoreactivity was decreased in METH-treated mice and increased in cocaine-treated mice. Neither cocaine nor METH could induce significant change in alpha-synuclein expression at the doses and duration we have used in the present study. CoQ10 treatment attenuated cocaine and METH-induced inhibition in the striatal 18F-DOPA uptake as determined by high-resolution microPET neuroimaging. Hence exogenous administration of CoQ10 may provide neuroprotection in drug addiction.
Klongpanichapak
Sirirat
S
Department of Pharmacology, Physiology and Therapeutics, School of Medicine & Health Sciences, University of North Dakota, 501 North Columbia Road, Grand Forks, ND, 58203, USA.
Govitrapong
Piyarat
P
Sharma
Sushil K
SK
Ebadi
Manuchair
M
D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003042:Cocaine / Q000633:toxicity*; D003067:Coenzymes; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015151:Immunoblotting; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051844:alpha-Synuclein / Q000096:biosynthesis
D000697:Central Nervous System Stimulants; D003067:Coenzymes; D017382:Reactive Oxygen Species; D051844:alpha-Synuclein; D014451:Ubiquinone; C043437:fluorodopa F 18; D008694:Methamphetamine; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; D042967:Electron Transport Complex I; C024989:coenzyme Q10; D003042:Cocaine; D004298:Dopamine