1-Methyl-4-phenyl-pyridinium (MPP+) uptake does not explain the differential toxicity of MPP+ in the nigrostriatal and mesolimbic dopaminergic pathways.
The present study examined the possible differential toxicity of 1-methyl-4-phenyl-pyridinium (MPP+) in the nigrostriatal and mesolimbic dopaminergic pathways in BALB/c mice, and investigated whether MPP+ uptake may account for this differential toxicity. Results indicated that chronic MPP+ infusions to the striatum (ST) and nucleus accumbens (NAc) both produced a toxicity on dopamine (DA) neurons. However, MPP+ produced a more severe DA depletion in the ST than in the NAc. Kinetic analyses from MPP+ uptake studies revealed a similar Km value in both the ST and NAc, suggesting that the affinity for MPP+ uptake is not different. The Vmax was approximately 1.6-fold higher in the ST than in the NAc. These results together suggest that chronic MPP+ infusions produce a differential toxicity on DA neurons in the nigrostriatal and mesolimbic dopaminergic pathways and that the ability of MPP+ uptake in DA terminals probably does not account for this differential toxicity.
Hung
H C
HC
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Tao
P L
PL
Lee
E H
EH
D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009434:Neural Pathways / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects*
D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine