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

Elisaveta Milusheva, M. Baranyi, Eszter Kormos, Zsuzsanna Hracskó, E. Vízi, B. Sperlágh

Research output: Contribution to journalArticle

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 - Mar 2010

Fingerprint

Antiparkinson Agents
Corpus Striatum
Rotenone
Dopamine
Oxidative Stress
Pharmaceutical Preparations
In Vitro Techniques
Selegiline
Poisons
Drug Design
Parkinson Disease
Adenosine Triphosphate

Keywords

  • Antiparkinsonian drugs
  • Dopamine release
  • HO
  • Oxidative stress
  • Rotenone
  • Striatum

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

The effect of antiparkinsonian drugs on oxidative stress induced pathological [3H]dopamine efflux after in vitro rotenone exposure in rat striatal slices. / Milusheva, Elisaveta; Baranyi, M.; Kormos, Eszter; Hracskó, Zsuzsanna; Vízi, E.; Sperlágh, B.

In: Neuropharmacology, Vol. 58, No. 4-5, 03.2010, p. 816-825.

Research output: Contribution to journalArticle

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