Influence of oxygen availability on the neurotoxic effect of 6-hydroxydopamine on nigro-striatal dopaminergic neurons.
The neurotoxin 6-hydroxydopamine (6-OHDA) was intracerebroventricularly injected (50 micrograms per mouse) in mice submitted to various oxygenation conditions and the striatal levels of dopamine (DA) and its metabolites were determined by HPLC 7 days later. In normoxic conditions the striatal depletion in DA reached 50%. This effect was not modified by a normobaric hypoxia (10% O2) applied 30 min before and 30 min after the 6-OHDA injection. On the contrary, the neurotoxic effect was reduced when the hypoxia was prolonged up to 11 h after the drug administration. When a normobaric hyperoxia (60% O2) was applied 30 min before and 11 h after the 6-OHDA injection, the neurotoxic effects of the latter were not modified. These data, as well as other results obtained from ex vivo experiments showing that normobaric hypoxia or hyperoxia did not modify the striatal synaptosomal [3H]DA uptake, indicate that oxygen availability does not exert a critical influence on the efficiency of the neuronal dopamine uptake complex.
Naudin
B
B
Unité de Neuropsychopharmacologie Expérimentale, URA CNRS 1170, Saint-Etienne du Rouvray, France.
Saligaut
C
C
Costentin
J
J
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001274:Atmospheric Pressure; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins; D006719:Homovanillic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D010100:Oxygen / Q000378:metabolism*; D013378:Substantia Nigra / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; C001746:3-methoxytyramine; D010100:Oxygen; D004298:Dopamine; D006719:Homovanillic Acid