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.
- Antiparkinsonian drugs
- Dopamine release
- Oxidative stress
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience