Basal ganglia neurotransmitter concentrations in rhesus monkeys following subchronic manganese sulfate inhalation

Background Manganese neurotoxicity in humans is recognized as a form of parkinsonism with lesions occurring predominantly within the globus pallidus, subthalamic nucleus, putamen, and caudate nucleus. Methods This study evaluated dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, serotonin, norepinephrine, 5-hydroxyindoleacetic acid, gamma-aminobutyric acid (GABA), and glutamate concentrations in the globus pallidus, caudate, and putamen of male rhesus monkeys exposed subchronically to either air or manganese sulfate (MnSO4) at 0.06, 0.3, or 1.5 mg Mn/m(3). Results An approximate 1.5-6-fold increase (vs. air-exposed controls) in mean brain manganese concentration was observed following subchronic MnSO4 exposure. A marginally significant (P < 0.1) decrease in pallidal GABA and 5-hydroxyindoleacetic acid concentration and caudate norepinephrine concentration occurred in monkeys exposed to MnSO4 at 1.5 mg Mn/m(3). Conclusions Despite the presence of increased tissue manganese concentrations, high-dose exposure to MnSO4 was associated with relatively few changes in basal ganglial neurotransmitter concentrations.