Acute interactions between L-DOPA and the neurotoxic effects of 1-methyl-4-phenylpyridinium or 6-hydroxydopamine in mice.
We have compared the effects of an i.p. pretreatment with L-DOPA (200 mg/kg) associated with benserazide (25 mg/kg) on neurotoxic effects of either 6-hydroxydopamine (6-OHDA) (50 microg, 10 microl per mouse) or 1-methyl-4-phenylpyridinium (MPP+) (17.5 microg, 10 microl per mouse). The striatal dopamine (DA) content, the vesicular monoamine transporter (VMAT2) density, as well as the hypothalamic norepinephrine (NE) content were measured 8 days after treatments. The L-DOPA-benserazide pretreatment worsened by 65% the 6-OHDA-induced depletion in striatal DA. On the contrary, it reduced by 42% the MPP+-induced depletion in striatal DA and by 54% the MPP+-induced decrease in VMAT2 density. It was noticed that the L-DOPA-benserazide pretreatment did not modify the marked decrease in hypothalamic NE content induced by 6-OHDA.
Cleren
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Unité de Neuropsychopharmacologie Expérimentale, UPRES-A CNRS 6036, IFRMP N 23, Site universitaire du Madrillet, Avenue de l'Université, 76800, Saint-Etienne du Rouvray, France.
Vilpoux
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Dourmap
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Bonnet
J J
JJ
Costentin
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J
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D001692:Biological Transport; D004347:Drug Interactions; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D009479:Neuropeptides; D009498:Neurotoxins / Q000633:toxicity*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D009498:Neurotoxins; D018377:Neurotransmitter Agents; C493453:Slc18a2 protein, mouse; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D007980:Levodopa; D016627:Oxidopamine; D015655:1-Methyl-4-phenylpyridinium; D009638:Norepinephrine