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Attenuation of Cocaine and Methamphetamine Neurotoxicity by Coenzyme Q10

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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

References

  1. Ritz MC, Boja JW, Grigoriadis D, Zaczek R, Carroll FI, Lewis AH, Kuhar MJ (1990) [3H]WIN 35,065–2: a ligand for cocaine receptors in striatum. J Neurochem 55:1556–1562

    Article  PubMed  CAS  Google Scholar 

  2. Cadet JL, Jayanthi S, Deng X (2003) Speed kills: cellular and molecular bases of methamphetamine-induced nerve terminal degeneration and neuronal apoptosis. FASEB J 17:1775–1788

    Article  PubMed  CAS  Google Scholar 

  3. Olanow CW, Tatton WG (1999) Etiology and pathogenesis of Parkinson’s disease. Annu Rev Neurosci 22:123–144

    Article  PubMed  CAS  Google Scholar 

  4. Oliveira MT, Rego AC, Morgadinho MT, Macedo TRA, Olivieira CR (2002) Toxic effects of opioid and stimulant drugs on undifferentiated PC12 cells. Ann NY Acad Sci 965:487–496

    Article  PubMed  CAS  Google Scholar 

  5. Menke T, Gille G, Reber F, Janetzky B, Andler W, Funk RH, Reichmann H (2003) CoenzymeQ10 reduces the toxicity of rotenone in neuronal cultures by preserving the mitochondrial membrane potential. Biofactors 18:65–72

    PubMed  CAS  Google Scholar 

  6. Sharma S, Kharadpezhou M, Shavali S, Refaey HEI, Eken J, Hagen C, Ebadi M (2004) Neuroprotective actions of Co Q10 in Parkinson’s disease. Meth Enzymol 382:488–509

    Article  PubMed  CAS  Google Scholar 

  7. Ebadi M, Brown-Borg H, Garrett S, Singh B, Shavali S, Sharma S (2005) Metallothionein-mediated neuroprotection in genetically-engineered mouse models of Parkinson’s disease. Mol Brain Res 134:67–75

    Article  PubMed  CAS  Google Scholar 

  8. Ebadi M, Sharma S, Wanpen S, Amornpan A (2004) Coenzyme Q10 inhibits mitochondrial complex-1 down regulation and nuclear factor-kappa B activation. J Cell Mol Med 8:213–222

    Article  PubMed  CAS  Google Scholar 

  9. Ebadi M, Govitrapong P, Sharma S, Muralikrishnan D, Shavali S, Pellett L, Schafer R, Albano C, Eken J (2001) Ubiquinone (Co Q10) and mitochondria in oxidative stress of Parkinson’s disease. Biol Signals Res 10:224–253

    Article  CAS  Google Scholar 

  10. Ebadi M, Sharma S (2003) Peroxynitrite and mitochondrial dysfunction in the pathogenesis of Parkinson’s disease. Antioxid Redox Signal 5:319–335

    Article  PubMed  CAS  Google Scholar 

  11. Sharma S, Ebadi M (2003) Metallothionein attenuates 3-morpholinosydnonimine (SIN-1)-induced oxidative stress in dopaminergic neurons. Antioxid Redox Signal 5:251–264

    Article  PubMed  CAS  Google Scholar 

  12. Sharma SK, Ebadi M (2004) An improved method for analyzing Co Q10 homologues and multiple detection of rare biological samples. J Neurosci Meth 137:1–8

    Article  CAS  Google Scholar 

  13. Zaragoza A, Diez-Fernandez C, Alvarez AM, Andres D, Cascales M (2000) Effect of N-acetylcysteine and deferoxamine on endogenous antioxidant defense system gene expression in a rat hepatocyte model of cocaine cytotoxicity. Biochim Biophys Acta 1496:183–195

    Article  PubMed  CAS  Google Scholar 

  14. Boess F, Ndikum-Moffor FM, Boeslsterli UA, Roberts SM (2000) Effects of cocaine and its oxidative metabolites on mitochondrial respiration and generation of reactive oxygen species. Biochem Pharmacol 60:615–623

    Article  PubMed  CAS  Google Scholar 

  15. Larsen KE, Fon EA, Hastings TG, Edwards RH, Sulzer D (2002) Methamphetamine-induced degeneration of dopaminergic neurons involves autophagy and upregulation of dopamine synthesis. J Neurosci 22:8951–8960

    PubMed  CAS  Google Scholar 

  16. Maragos WF, Jakel R, Chesnut D, Pocernich CB, Butterfield DA, St Clair S, Cass WA (2000) Methamphetamine toxicity is attenuated in mice that overexpress human manganese superoxide dismutase. Brain Res 878:218–222

    Article  PubMed  CAS  Google Scholar 

  17. Gluck MR, Moy LY, Jayatilleke E, Hogan KA, Manzino L, Sonsalla PK (2001) Parallel increases in lipid and protein oxidative markers in several mouse brain regions after methamphetamine treatment. J Neurochem 79:152–160

    Article  PubMed  CAS  Google Scholar 

  18. Dietrich JB, Mangeol A, Revel MO, Burgun C, Aunis D, Zwiller J (2005) Acute or repeated cocaine administration generates reactive oxygen species and induces antioxidant enzyme activity in dopaminergic rat brain structures. Neuropharmacology 48:965–974

    Article  PubMed  CAS  Google Scholar 

  19. Jayanthi S, Deng X, Noailles PH, Ladenheim B, Cadet JL (2004) Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades. FASEB J 18:238–251

    Article  PubMed  CAS  Google Scholar 

  20. Burrows KB, Gudelsky G, Yamamoto BK (2000) Rapid and transient inhibition of mitochondrial function following methamphetamine or 3,4-methylenedioxymethamphetamine administration. Eur J Pharmacol 398:11–18

    Article  PubMed  CAS  Google Scholar 

  21. Dietrich JB, Poirier R, Aunis D, Zwiller J (2004) Cocaine downregulates the expression of the mitochondrial genome in rat brain. Ann NY Acad Sci 1025:345–350

    Article  PubMed  CAS  Google Scholar 

  22. Brenz Verca MS, Bahi A, Boyer F, Wagner GC, Dreyer JL (2003) Distribution of α- and γ-synucleins in the adult rat brain and their modification by high-dose cocaine treatment. Eur J Neurosci 18:1923–1938

    Article  PubMed  Google Scholar 

  23. Sorg BA, Chen SY, Kalivas PW (1993) Time course of tyrosine hydroxylase expression after behavioral sensitization to cocaine. J Pharmacol Exp Ther 266:424–430

    PubMed  CAS  Google Scholar 

  24. Cappon GD, Morford LL, Vorhees CV (1998) Enhancement of cocaine-induced hyperthermia fails to elicit neurotoxicity. Neurotoxicol Teratol 20:531–535

    Article  PubMed  CAS  Google Scholar 

  25. Xie T, Tong L, Barrett T, Yuan J, Hatzidimitriou G, McCann UD, Becker KG, Donovan DM, Ricaurte GA (2002) Changes in gene expression linked to methamphetamine-induced dopaminergic neurotoxicity. J Neurosci 22:274–283

    PubMed  CAS  Google Scholar 

  26. Sharma S, Ebadi M (2005) Distribution kinetics of 18F-DOPA in weaver mutant mice. Mol Brain Res 139:23–30

    Article  PubMed  CAS  Google Scholar 

  27. Bowyer JF, Frame LT, Clausing P, Nagamoto-Combs K, Osterhout CA, Sterling CR, Tank AW (1998) Long-term effects of amphetamine neurotoxicity on tyrosine hydroxylase mRNA and protein in aged rats. J Pharmacol Exp Ther 286:1074–1085

    PubMed  CAS  Google Scholar 

  28. Beitner-Johnson D, Nestler EJ (1991) Morphine and cocaine exert common chronic actions on tyrosine hydroxylase in dopaminergic brain reward regions. J Neurochem 57:344–347

    Article  PubMed  CAS  Google Scholar 

  29. Vrana SL, Vrana KE, Koves TR, Smith JE, Dworkin SI (1993) Chronic cocaine administration increases CNS tyrosine hydoxylase enzyme activity and mRNA levels and tryptrophan hydroxylase enzyme activity levels. J Neurochem 61:2262–2268

    Article  PubMed  CAS  Google Scholar 

  30. Masserano JM, Baker I, Natsukari N, Wyatt RJ (1996) Chronic cocaine administration increases tyrosine hydroxylase activity in the ventral tegmental area through glutaminergic- and dopaminergic D2-receptor mechanisms. Neurosci Lett 217:73–76

    Article  PubMed  CAS  Google Scholar 

  31. Lu L, Grimm JW, Shaham Y, Hope BT (2003) Molecular neuroadaptations in the accumbens and ventral tegmental area during the first 90 days of forced abstinence from cocaine self-administration in rats. J Neurochem 85:1604–1613

    Article  PubMed  CAS  Google Scholar 

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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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Authors and Affiliations

  1. Department of Pharmacology, Physiology and Therapeutics, School of Medicine & Health Sciences, University of North Dakota, 501 North Columbia Road, Grand Forks, ND, 58203, USA

    Sirirat Klongpanichapak & Manuchair Ebadi

  2. Neuro-Behavioural Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya, 73170, Nakornpathom, Thailand

    Sirirat Klongpanichapak & Piyarat Govitrapong

  3. Center for Neuroscience and Department of Pharmacology, Faculty of Science, Mahidol University, Rama VI Road, 10400, Bangkok, Thailand

    Piyarat Govitrapong

  4. Department of Pathology, University of North Dakota, Grand Forks, ND, 58203, USA

    Sushil K. Sharma

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  1. Sirirat Klongpanichapak
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  2. Piyarat Govitrapong
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  3. Sushil K. Sharma
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  4. Manuchair Ebadi
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Correspondence to Manuchair Ebadi.

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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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