Consequences of manganese administration for striatal dopamine and motor behavior in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-exposed C57BL/6 mice

• Published in: Human & experimental toxicology 2013-08, Vol.32 (8), p.865-880
• Main Authors: Dodd, C.A., Bloomquist, J.R., Klein, B.G.
• Format: Article
• Language: English
• Subjects: 3,4-Dihydroxyphenylacetic Acid - metabolism; Animals; Basal ganglia; Behavior, Animal - drug effects; Biomedical research; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dopamine; Dopamine - metabolism; Drug Interactions; Male; Manganese - administration & dosage; Manganese - toxicity; Mice; Mice, Inbred C57BL; Motor ability; Motor Activity - drug effects; MPTP Poisoning - metabolism; MPTP Poisoning - physiopathology; Mutagenesis; Parkinson's disease
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/0960327112469043

Environmental compounds may be important contributors to Parkinson’s disease etiology. Epidemiological and experimental evidence for the facilitation of parkinsonism by manganese is equivocal. This work addressed methodological concerns in the few studies of manganese modulation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in C57BL/6 mice. Male, retired breeder mice received 0 or 100 mg/kg of manganese chloride (MnCl2; subcutaneously on days 1, 4 and 7) and 0 or 20 mg/kg of MPTP (intraperitoneally on day 8) and survived up to day 15 or 22. On the day of sacrificing, horizontal (grid crossing) and vertical (rearing) open field movement, swimming, grip strength and grip fatigue were examined. Striata were analyzed for dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) using high-performance liquid chromatography. MPTP produced a main effect decrease in striatal dopamine (48.8%) and DOPAC (38.1%), but there was no main effect of MnCl2 or MnCl2 × MPTP interaction. However, modulatory interactions were observed between the effects of MnCl2 and MPTP for grid crossing, rearing and grip strength. Interestingly, these interactions reduced the severity of behavioral deficits attributable to either of these compounds alone. For rearing and grip strength, the MnCl2 × MPTP interaction was dependent upon survival time. The mechanistic nature of the MnCl2 × MPTP interaction upon these behaviors, in the absence of such an interaction for striatal dopamine and DOPAC, remains to be clarified.