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 th at Mn concentration in the central nervous system (CNS), particularly in th e ventral mesencephalon, is decreased by inhibiting dopamine reuptake using cocaine or by decreasing dopamine concentrations using reserpine. The intr athecal administration of Mn (250 mu g Mn/rat as MnCl2) caused the Mn conce ntration in the ventral mesencephalon to increase from 0.57 to 31.8 mu g Mn /g. Cocaine administration (8.6 mg/kg i.p.) thirty minutes prior to MnCl2 d ecreased ventral mesencephalon Mn to 3.3 mu g Mn/g. By giving reserpine (5 mg/kg i.p.) 24 hours prior to MnCl2 the ventral mesencephalon Mn concentrat ion was decreased from 29.9 mu g Mn/g to 3.7 mu g Mn/g. Intrathecal MnCl2 d ecreased 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 puta men 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 re gions can be inhibited by cocaine, a dopamine reuptake inhibitor, or by res erpine, a dopamine depleter, and suggest that the Mn concentration in the C NS is related to dopamine reuptake and/or concentration. (C) 1999 Inter Pre ss, Inc.