Dopamine transporters are involved in the onset of hypoxia-induced dopamine efflux in striatum as revealed by in vivo microdialysis.
Although many studies have revealed alterations in neurotransmission during ischaemia, few works have been devoted to the neurochemical effects of mild hypoxia, a situation encountered during life in altitude or in several pathologies. In that context, the present work was undertaken to determine the in vivo mechanisms underlying the striatal dopamine efflux induced by mild hypoxaemic hypoxia. For that purpose, the extracellular concentrations of dopamine and its metabolite 3,4-dihydroxyphenyl acetic acid were simultaneously measured using brain microdialysis during acute hypoxic exposure (10% O(2), 1h) in awake rats. Hypoxia induced a +80% increase in dopamine. Application of the dopamine transporters inhibitor, nomifensine (10 microM), just before the hypoxia prevented the rise in dopamine during the early part of hypoxia; in contrast the application of nomifensine after the beginning of hypoxia, failed to alter the increase in dopamine. Application of the voltage-dependent Na(+) channel blocker tetrodotoxin abolished the increase in dopamine, whether administered just before or after the beginning of hypoxia. These data show that the neurochemical mechanisms of the dopamine efflux may change over the course of the hypoxic exposure, dopamine transporters being involved only at the beginning of hypoxia.
Orset
Cyrille
C
Laboratoire de Neuropharmacologie et Neurochimie, IFR 19, Faculté de Pharmacie, Université Claude Bernard, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France.
Parrot
Sandrine
S
Sauvinet
Valérie
V
Cottet-Emard
Jean-Marie
JM
Bérod
Anne
A
Pequignot
Jean-Marc
JM
Denoroy
Luc
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D045604:Extracellular Fluid / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017551:Microdialysis; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009627:Nomifensine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D026941:Sodium Channel Blockers; D015102:3,4-Dihydroxyphenylacetic Acid; D009627:Nomifensine; D004298:Dopamine