Central nervous system toxicity of manganese. II: Cocaine or reserpine inhibit manganese concentration in the rat brain.
Manganese concentrates in the ventral mesencephalon of male Sprague-Dawley rats after intrathecal administration of MnCl2. We tested the hypothesis that Mn concentration in the central nervous system (CNS), particularly in the ventral mesencephalon, is decreased by inhibiting dopamine reuptake using cocaine or by decreasing dopamine concentrations using reserpine. The intrathecal administration of Mn (250 micrograms Mn/rat as MnCl2) caused the Mn concentration in the ventral mesencephalon to increase from 0.57 to 31.8 micrograms Mn/g. Cocaine administration (8.6 mg/kg i.p.) thirty minutes prior to MnCl2 decreased ventral mesencephalon Mn to 3.3 micrograms Mn/g. By giving reserpine (5 mg/kg i.p.) 24 hours prior to MnCl2 the ventral mesencephalon Mn concentration was decreased from 29.9 micrograms Mn/g to 3.7 micrograms Mn/g. Intrathecal MnCl2 decreased the dopamine concentration in the caudate putamen by 40% six hours after administration. Cocaine or reserpine decreased the Mn concentration in the ventral mesencephalon, occipital pole, frontal lobe and caudate putamen but did not change the Mn concentration in the cerebellum. The results indicate that the mechanism(s) by which Mn is concentrated in many brain regions can be inhibited by cocaine, a dopamine reuptake inhibitor, or by reserpine, a dopamine depleter, and suggest that the Mn concentration in the CNS is related to dopamine reuptake and/or concentration.
Ingersoll
R T
RT
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721, USA.
Montgomery
E B
EB
Aposhian
H V
HV
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000493:pharmacokinetics*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D008345:Manganese / Q000493:pharmacokinetics; D020149:Manganese Poisoning; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology*; D013054:Spectrophotometry, Atomic; D013997:Time Factors
D018759:Adrenergic Uptake Inhibitors; D018765:Dopamine Uptake Inhibitors; D008345:Manganese; D012110:Reserpine; D003042:Cocaine; D004298:Dopamine