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 ext racellular dopamine (DA). The present work investigated whether DA accumula tion is related to a glutamatergic mechanism and/or production of reactive oxygen species (ROS) in the striatum. Concentrations of extracellular DA, g lutamate and hydroxyl radicals (. OH) were measured in the presence or abse nce of an N-methyl-D-aspartate (NMDA) receptor blocker (dizocilpine, MK-801 ) or an antioxidant (Trolox). Measurements were performed using high-perfor mance Liquid chromatography (HPLC) with electrochemical and fluorimetric de tection on samples obtained by an in vivo microdialysis perfusion technique and stored at -80 degrees C. The increase in lactic acid-induced DA was en tirely suppressed by MK-801 and Trolox. Lactacidosis also induced an increa se in extracellular glutamate and . OH concentrations at the same time as t he first DA accumulation, as well as another . OH accumulation which preced ed and accompanied the second DA concentration peak. Glutamate release was totally inhibited by MK-801 or Trolox. The first peak of . OH production wa s completely suppressed by MK-801 and Trolox, but the second one was only s uppressed by Trolox. These data showed that the increase in DA induced by l actic acid was related to glutamatergic excitotoxicity and ROS production, suggested that the kinetic of events was different for the two DA accumulat ions. (C) 1999 Elsevier Science B.V. All rights reserved.