Central nervous system toxicity of manganese. I. Inhibition of spontaneous motor activity in rats after intrathecal administration of manganese chloride.
The intrathecal administration of MnCl2 to young male rats caused dopamine depletion in the caudate-putamen and a decrease in spontaneous motor activity. Our experiments demonstrate that in the young rat: (a) the lateral choroid plexus protects the cerebrospinal fluid (CSF) from high concentrations of Mn in the blood by sequestering and thus preventing large amounts of this metal ion from entering the CSF. As blood Mn levels rise, the lateral choroid plexus may become overwhelmed and leak an increasing amount of Mn into the CSF. (b) The lateral choroid plexus does not remove Mn2+ from the CSF. (c) The injection of MnCl2 into the CSF of rats caused a rapid decrease in spontaneous motor activity which is dose-dependent and reversible under the present experimental conditions. Intrathecal Mn results in a substantial decrease in striatal dopamine but not homovanillic acid or 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations and is associated with an increase in the Mn concentration of the substantia nigra and caudate-putamen.
Ingersoll
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RT
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85724, USA.
Montgomery
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EB
Aposhian
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HV
D000818:Animals; D001923:Brain Chemistry; D002490:Central Nervous System / Q000187:drug effects*; D002712:Chlorides / Q000008:administration & dosage / Q000633:toxicity*; D002831:Choroid Plexus / Q000502:physiology*; D004298:Dopamine / Q000032:analysis; D007278:Injections, Spinal; D008297:Male; D008345:Manganese / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D017895:Manganese Compounds / Q000008:administration & dosage; D020149:Manganese Poisoning; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000737:chemistry
D002712:Chlorides; D017895:Manganese Compounds; D008345:Manganese; C025340:manganese chloride; D004298:Dopamine