Manganese neurotoxicity: effects of L-DOPA and pargyline treatments.
Single, monolateral injection into rat substantia nigra of manganese chloride produced within two weeks from its administration a loss of dopamine in the striatum ipsilateral to the injected side. The effect was dose-dependent and was not extended to serotoninergic terminals present in this brain area, whose content in serotonin and 5-hydroxyindoleacetic acid was not affected. When L-DOPA + carbidopa or pargyline were given to these animals the decrease of striatal dopamine was more marked. Moreover, rats treated two weeks before with a dose of manganese chloride that produced a 70-80% drop in striatal dopamine concentrations, rotated ipsilaterally to the dopamine-depleted striatum when injected with apomorphine, suggesting that in these animals the stimulatory effects of apomorphine were more relevant in striatum where presynaptic dopaminergic neurons were not affected by manganese chloride. These data indicate that the alterations of dopaminergic postsynaptic receptors may be different in parkinsonian and in manganese-intoxicated patients and that current therapy used for Parkinson's disease could be a hazard in treating manganese poisoning.
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Groppetti
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001480:Basal Ganglia Diseases / Q000139:chemically induced*; D003342:Corpus Striatum / Q000032:analysis; D004298:Dopamine / Q000032:analysis; D004357:Drug Synergism; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D007980:Levodopa / Q000633:toxicity*; D008297:Male; D020149:Manganese Poisoning; D010293:Pargyline / Q000633:toxicity*; D010300:Parkinson Disease / Q000188:drug therapy; D051381:Rats; D012701:Serotonin / Q000032:analysis
D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D010293:Pargyline; D004298:Dopamine