Selective lesion of the nigrostriatal dopaminergic pathway by MPTP and acetaldehyde or diethyldithiocarbamate.
We have previously reported that diethyldithiocarbamate and acetaldehyde enhance MPTP toxicity in mice (Corsini et al. 1986). Here we show that these drugs enhance the depletion of dopamine in the striatum and markedly increase MPTP-induced death of DA neurons in the substantia nigra. This enhancement of MPTP toxicity is specific for the nigro-striatal DA pathway and no recovery occurs, at least for four months after the treatment. Rats, although they show an MPTP-induced acute syndrome similar to the that induced in mice by the combined treatments, appear to be insensitive to both MPTP alone or to combined treatment with diethyldithiocarbamate or acetaldehyde. The selectivity of the permanent bilateral lesions of the nigro-striatal pathway make mice treated with acetaldehyde or diethyldithiocarbamate and MPTP a simple and reliable model for parkinsonism.
Zuddas
A
A
Institute of Pharmacology, School of Medicine, University of Pisa, Italy.
Vaglini
F
F
Fornai
F
F
Corsini
G U
GU
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects*; D004050:Ditiocarb / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D004050:Ditiocarb; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D000079:Acetaldehyde; D004298:Dopamine