Lactic acid-induced increase of extracellular dopamine measured by microdialysis in rat striatum: evidence for glutamatergic and oxidative mechanisms.
Striatal lactacidosis was induced by direct lactic acid perfusion to obtain a local pH as close as possible to that observed in ischemia. In a previous study we showed that such lactacidosis produces a diphasic increase in extracellular dopamine (DA). The present work investigated whether DA accumulation is related to a glutamatergic mechanism and/or production of reactive oxygen species (ROS) in the striatum. Concentrations of extracellular DA, glutamate and hydroxyl radicals ((.)OH) were measured in the presence or absence of an N-methyl-D-aspartate (NMDA) receptor blocker (dizocilpine, MK-801) or an antioxidant (Trolox). Measurements were performed using high-performance liquid chromatography (HPLC) with electrochemical and fluorimetric detection on samples obtained by an in vivo microdialysis perfusion technique and stored at -80 degrees C. The increase in lactic acid-induced DA was entirely suppressed by MK-801 and Trolox. Lactacidosis also induced an increase in extracellular glutamate and (.)OH concentrations at the same time as the first DA accumulation, as well as another (.)OH accumulation which preceded and accompanied the second DA concentration peak. Glutamate release was totally inhibited by MK-801 or Trolox. The first peak of (.)OH production was completely suppressed by MK-801 and Trolox, but the second one was only suppressed by Trolox. These data showed that the increase in DA induced by lactic acid was related to glutamatergic excitotoxicity and ROS production, suggested that the kinetic of events was different for the two DA accumulations.
Remblier
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Centre d'Etudes et de Recherche sur les Xénobiotiques (UPRES EA 1223), Faculté de Médecine et de Pharmacie, B.P. 199, 34, rue du Jardin des Plantes, 86005, Poitiers Cedex, France.
Pontcharraud
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Tallineau
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Piriou
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Huguet
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F
D000140:Acidosis, Lactic / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry / Q000379:methods; D005841:Gentisates; D018698:Glutamic Acid / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D007700:Kinetics; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D002839:Chromans; D005841:Gentisates; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; D019344:Lactic Acid; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; C010925:2,5-dihydroxybenzoic acid; D004298:Dopamine