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

• Published in: Neuropharmacology Vol. 58; no. 4; pp. 816 - 825
• Main Authors: Milusheva, Elisaveta, Baranyi, Mária, Kormos, Eszter, Hracskó, Zsuzsanna, Sylvester Vizi, E., Sperlágh, Beáta
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2010
• Subjects: Animals; Antiparkinson Agents - pharmacology; Antiparkinsonian drugs; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - pathology; Dopamine - metabolism; Dopamine release; H 2O 2; Male; Organ Culture Techniques; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; PC12 Cells; Rats; Rats, Wistar; Rotenone; Rotenone - pharmacology; Striatum; H 2O 2; Oxidative stress; Striatum; Dopamine release; Antiparkinsonian drugs; Rotenone
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2009.11.017

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 H 2O 2-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 H 2O 2-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 H 2O 2-evoked and electrically-induced [ 3H]dopamine efflux. Furthermore, l-DOPA promoted the formation of dopamine quinone. Ropinirole (100 nM) did not affect resting and H 2O 2-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 H 2O 2-evoked [ 3H]dopamine efflux. Rasagiline (0.01–50 μM) slightly inhibited H 2O 2-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 H 2O 2-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.