The effect of antiparkinsonian drugs on oxidative stress induced pathological [3H]dopamine efflux after in vitro rotenone exposure in rat striatal slices

Elisaveta Milusheva, Mária Baranyi, Eszter Kormos, Zsuzsanna Hracskó, E. Sylvester Vizi, Beáta Sperlágh

Research output: Article

13 Citations (Scopus)

Abstract

An in vitro model of mitochondrial dysfunction with subsequent oxidative stress was elaborated and utilized to study the effect of drugs, currently used for the treatment of Parkinson's disease, on pathological H2O2-evoked [3H]dopamine efflux and the formation of toxic dopamine metabolites in rat striatal slices. 60 min rotenone (0.1-10 μM) pretreatment decreased dopamine content and [3H]dopamine uptake, as well as ATP level and energy charge of the slices. In addition, a robust potentiation of H2O2-evoked [3H]dopamine efflux and the formation of dopamine quinone in the effluent was detected. l-DOPA (200 μM) markedly elevated resting but not 100 μM H2O2-evoked and electrically-induced [3H]dopamine efflux. Furthermore, l-DOPA promoted the formation of dopamine quinone. Ropinirole (100 nM) did not affect resting and H2O2-evoked [3H]dopamine efflux and inhibited the electrically evoked release only in untreated slices. l-deprenyl, at concentration of 0.01 μM potentiated, whilst between 1 and 50 μM diminished H2O2-evoked [3H]dopamine efflux. Rasagiline (0.01-50 μM) slightly inhibited H2O2-evoked [3H]dopamine efflux, and it was able to prevent the generation of dopamine quinone. Neither of the drugs was able to suppress both the pathological H2O2-evoked [3H]dopamine efflux and the formation of dopamine quinone with simultaneous augmentation of electrically evoked [3H]dopamine release what should be a future concept of antiparkinsonian drug-design.

Original languageEnglish
Pages (from-to)816-825
Number of pages10
JournalNeuropharmacology
Volume58
Issue number4-5
DOIs
Publication statusPublished - márc. 1 2010

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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