L-DOPA-induced 6-hydroxydopamine production in the striata of rodents is sensitive to the degree of denervation

Neurochemistry International
Anupom Borah, K P Mohanakumar

Abstract

We tested the hypothesis that long-term l-DOPA treatment in Parkinson's disease (PD) would result in increased production of the dopamine oxidation product, 6-hydroxydopamine (6-OHDA) in the striatum. We administered L-DOPA (250 mg/kg) by gavation for 3 days following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg, i.p., twice, 16 h apart) in mice or for 30 days in rats which received 1-methyl-4-phenylpyridinium ion (MPP(+); 16 nmol/1 microl) unilaterally in median forebrain bundle, and measured 6-OHDA in the striatum using a sensitive HPLC-electrochemical detection procedure. While the contralateral innervated striatum of rats showed no difference, a significant increase in 6-OHDA level in the denervated (>85% dopamine depletion) ipsilateral striatum was observed. Partial nigrostriatal denervation with a lower dose of MPP(+) (8 nmol/1 microl) in rats or following sub-acute MPTP treatment in mice failed to cause any significant change in 6-OHDA level following several doses of L-DOPA administration. Since a single dose of MPTP (30 mg/kg, i.p.) or L-deprenyl (0.25 mg/kg, i.p.) in L-DOPA primed (250 mg/kg daily for 7 days) mice caused significant increase in 6-OHDA in the striatum, augmentation of reactive oxygen sp...Continue Reading

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Citations

May 14, 2010·Journal of Bioenergetics and Biomembranes·Mritunjay PandeyRajamma Usha
Aug 13, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Jill K MorrisPaige C Geiger
Aug 2, 2015·Neurochemistry International·Rajib PaulAnupom Borah
Oct 15, 2013·CNS Neuroscience & Therapeutics·Anupom BorahKochupurackal P Mohanakumar
Jul 5, 2011·Progress in Neurobiology·Janusz LipskiNicola B Mercuri
Jun 19, 2016·Biochimica Et Biophysica Acta·Rajib Paul, Anupom Borah
Jan 16, 2021·Chemico-biological Interactions·Igor PanticClaude Brodski

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