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Publication Detail

Title: Chronic exposure to manganese alters brain responses to amphetamine: a pharmacological magnetic resonance imaging study.

Authors: Williams, Jason M; Milatovic, Dejan; Gore, John C; Aschner, Michael; Avison, Malcolm J

Published In Toxicol Sci, (2010 Apr)

Abstract: The parkinsonian symptoms and increased Mn accumulation in dopaminergic (DAergic) neurons of the basal ganglia implicate impaired dopamine signaling in the neurotoxic effects of chronic manganese overexposure. Using blood oxygenation level-dependent (BOLD) pharmacological magnetic resonance imaging (phMRI), we mapped brain responses to acute amphetamine (AMPH; 3 mg/kg, ip), which stimulates midbrain DAergic systems, in male Sprague-Dawley rats following 6 weeks of chronic MnCl(2) (5 mg Mn/kg, one per week, iv) or saline treatment. Plasma Mn content, measured immediately following phMRI, was elevated twofold in Mn-treated animals (p < 0.05), but the twofold increase in mean striatal Mn content did not reach significance. In saline-treated animals, AMPH stimulated robust positive BOLD responses throughout the basal ganglia and their reciprocally innervated connections. In contrast, acute AMPH stimulated a negative BOLD response in many of these structures in the Mn-treated group, resulting in significant differences between saline- and Mn-treated AMPH-evoked BOLD responses within caudate putamen, globus pallidus, substantia nigra, mediodorsal thalamic nucleus, and somatosensory cortex. These results demonstrate the utility of AMPH-evoked phMRI as readout of the DAergic signaling in vivo and confirm the vulnerability of DAergic systems to Mn.

PubMed ID: 20061340 Exiting the NIEHS site

MeSH Terms: Amphetamine/pharmacology*; Animals; Brain Mapping; Brain/drug effects*; Brain/metabolism; Brain/pathology; Chlorides/blood; Chlorides/toxicity*; Dopamine Uptake Inhibitors/pharmacology*; Drug Antagonism; Injections, Intravenous; Magnetic Resonance Imaging/methods*; Male; Manganese Compounds/blood; Oxygen/blood; Rats; Rats, Sprague-Dawley

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