Abstract
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 α-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.
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Abbreviations
- CoQ10 :
-
coenzyme Q10
- DOPAC:
-
dihydroxy phenyl acetic acid
- DA:
-
dopamine
- 18F-DOPA:
-
18F-fluoro-dihydroxyphenylalanine
- wv/wv mice:
-
homozygous weaver mutant mice
- METH:
-
methamphetamine
- MPTP:
-
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- MAO:
-
mono amine oxidase
- NFκβ:
-
nuclear factor kappa-B
- NS-DA-ergic:
-
nigrostriatal dopaminergic
- PBS:
-
phosphate-buffered saline
- OSEM:
-
ordered subset expectation maximization
- ROS:
-
reactive oxygen species
- SDS-PAGE:
-
sodium dodecyl sulphate polyacrylamide gel electrophoresis
- SCADA:
-
supervisory control & documentation analysis
- TBARs:
-
thiobarbituric acid reactive substances
- BS:
-
Tris-buffered saline
- TH:
-
tyrosine hydroxylase
- VMAT-2:
-
vesicular monoamine transporters
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Acknowledgements
These studies were supported in part from a grant on “Dopaminergic transmissions and their roles in drug addiction” provided by Counter Drug Technology Center, Office of National Drug Control Policy #DATM05-02-C-1252 (M.E). Sirirat Klongpanichapak is the recipient of the Thai Royal Golden Jubilee (Ph.D. Program) provided by the Thailand Research Fund. The authors express their appreciation for the excellent skills of Dani Stramer for typing this manuscript.
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Klongpanichapak, S., Govitrapong, P., Sharma, S.K. et al. Attenuation of Cocaine and Methamphetamine Neurotoxicity by Coenzyme Q10 . Neurochem Res 31, 303–311 (2006). https://doi.org/10.1007/s11064-005-9025-3
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DOI: https://doi.org/10.1007/s11064-005-9025-3