Recovery of motor function and dopaminergic parameters in a mouse model of Parkinson's disease induced by co-administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and diethyldithiocarbamate.
Diethyldithiocarbamate (DDC) enhances the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We studied the time course of dopaminergic parameters and motor function of MPTP+DDC-lesioned C57BL/6 mice, a model of Parkinson's disease. MPTP+DDC-lesioned mice showed a decrease in dopamine (DA) and its metabolites contents in their striata 1, 3 and 6 weeks after MPTP+DDC-treatment, compared with those of each control group. The partial and significant recoveries in DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid contents were also observed after 6 weeks, compared with those at 1 week after treatment. In addition, bradykinesia due to DA depletion was observed in mice 1 week after MPTP+DDC-treatment, but it was not significant 3 weeks after the treatment. l-DOPA alone and a co-administration of l-DOPA and a monoamine oxidase-B inhibitor selegiline improved bradykinesia of this model, also suggesting that bradykinesia observed in the model was mediated to dopaminergic deficiency. On the other hand, the serotonin content increased slightly but significantly after 3 or 6 weeks, suggesting compensatory activation of the serotonergic system against DA depletion. Thus, the partial recovery of dopaminergic parameters, the recovery of motor function and the compensatory activation of the serotonergic system were observed in this model 3-6 weeks after MPTP+DDC treatment.
Shimazu
S
S
Research Institute, Fujimoto Pharmaceutical Corporation, Osaka, Japan. soyaku@fujimoto-pharm.co.jp
Takahata
K
K
Tamashiro
A
A
Yoneda
F
F
Iida
Y
Y
Saji
H
H
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004050:Ditiocarb / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D006719:Homovanillic Acid / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D012701:Serotonin; D007980:Levodopa; D004050:Ditiocarb; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid