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Rotenone increases glutamate-induced dopamine release but does not affect hydroxyl-free radical formation in rat striatum.
Synapse. 2003 Dec 01; 50(3):240-50.S

Abstract

Impairment of the mitochondrial complex I has been found in Parkinson's disease and recently long-term treatment with the complex I inhibitor rotenone led to neurodegeneration and Lewy body-like inclusions in rats. To investigate the relationship of free radical formation, complex I inhibition, and dopamine release, rotenone (15 mg/kg s.c.) was injected in male Sprague Dawley rats. Complex I inhibition was measured in the striatum and substantia nigra using the lactate accumulation assay. Dopamine release and free radical formation was determined using striatal microdialysis in combination with the salicylate hydroxylation assay. In a second experiment, glutamate (10 mM) stimulation via the microdialysis probe was used to provoke hydroxyl radical formation and dopamine release 60 min after rotenone or vehicle pretreatment. Rotenone significantly increased striatal and nigral lactate levels. However, rotenone did not produce a significant increase in hydroxyl radical formation and dopamine release, but led to a pronounced hypokinesia. In contrast, rotenone in comparison to vehicle pretreatment produced a significant augmentation of glutamate-induced dopamine release (67-fold and 31-fold increase, respectively) and did not affect the glutamate-induced hydroxyl free radical formation (23-fold and 21-fold increase, respectively). The present study demonstrates that a single systemic rotenone administration does not lead to neurotoxicity, but rather to enhanced glutamate-induced dopamine release with no further increase of hydroxyl free radical formation. Thus, acute complex I inhibition in the presence or absence of high extracellular dopamine and glutamate levels is not critically involved in the formation of hydroxyl free radicals.

Authors+Show Affiliations

Behavioral Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, CH-8603 Schwerzenbach, Switzerland.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14515342

Citation

Leng, Andreas, et al. "Rotenone Increases Glutamate-induced Dopamine Release but Does Not Affect Hydroxyl-free Radical Formation in Rat Striatum." Synapse (New York, N.Y.), vol. 50, no. 3, 2003, pp. 240-50.
Leng A, Feldon J, Ferger B. Rotenone increases glutamate-induced dopamine release but does not affect hydroxyl-free radical formation in rat striatum. Synapse. 2003;50(3):240-50.
Leng, A., Feldon, J., & Ferger, B. (2003). Rotenone increases glutamate-induced dopamine release but does not affect hydroxyl-free radical formation in rat striatum. Synapse (New York, N.Y.), 50(3), 240-50.
Leng A, Feldon J, Ferger B. Rotenone Increases Glutamate-induced Dopamine Release but Does Not Affect Hydroxyl-free Radical Formation in Rat Striatum. Synapse. 2003 Dec 1;50(3):240-50. PubMed PMID: 14515342.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rotenone increases glutamate-induced dopamine release but does not affect hydroxyl-free radical formation in rat striatum. AU - Leng,Andreas, AU - Feldon,Joram, AU - Ferger,Boris, PY - 2003/9/30/pubmed PY - 2004/1/7/medline PY - 2003/9/30/entrez SP - 240 EP - 50 JF - Synapse (New York, N.Y.) JO - Synapse VL - 50 IS - 3 N2 - Impairment of the mitochondrial complex I has been found in Parkinson's disease and recently long-term treatment with the complex I inhibitor rotenone led to neurodegeneration and Lewy body-like inclusions in rats. To investigate the relationship of free radical formation, complex I inhibition, and dopamine release, rotenone (15 mg/kg s.c.) was injected in male Sprague Dawley rats. Complex I inhibition was measured in the striatum and substantia nigra using the lactate accumulation assay. Dopamine release and free radical formation was determined using striatal microdialysis in combination with the salicylate hydroxylation assay. In a second experiment, glutamate (10 mM) stimulation via the microdialysis probe was used to provoke hydroxyl radical formation and dopamine release 60 min after rotenone or vehicle pretreatment. Rotenone significantly increased striatal and nigral lactate levels. However, rotenone did not produce a significant increase in hydroxyl radical formation and dopamine release, but led to a pronounced hypokinesia. In contrast, rotenone in comparison to vehicle pretreatment produced a significant augmentation of glutamate-induced dopamine release (67-fold and 31-fold increase, respectively) and did not affect the glutamate-induced hydroxyl free radical formation (23-fold and 21-fold increase, respectively). The present study demonstrates that a single systemic rotenone administration does not lead to neurotoxicity, but rather to enhanced glutamate-induced dopamine release with no further increase of hydroxyl free radical formation. Thus, acute complex I inhibition in the presence or absence of high extracellular dopamine and glutamate levels is not critically involved in the formation of hydroxyl free radicals. SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/14515342/Rotenone_increases_glutamate_induced_dopamine_release_but_does_not_affect_hydroxyl_free_radical_formation_in_rat_striatum_ L2 - https://doi.org/10.1002/syn.10260 DB - PRIME DP - Unbound Medicine ER -