Depletion of striatal dopamine by the N-oxide of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
The N-oxide of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the major metabolite found in vivo and excreted in urine after the parenteral administration of the neurotoxicant, MPTP. In mice (C57BL/6), stereotaxic injection of MPTP N-oxide (15 micrograms) into the neostriatum produced dopamine (DA) depletion similar to that caused by MPTP. The DA depleting effect of MPTP N-oxide was a direct action, whereas the action of MPTP was mediated by the generation of oxidative metabolites. In the mouse striatal synaptosomal preparation, MPTP, MPP+ and MPTP N-oxide all competed with [3H]DA at its uptake site. In addition, MPP+ and MPTP N-oxide promoted [3H]DA release. In contrast to MPTP and MPDP+, MPTP N-oxide did not alter the electrophysiologically recorded field potential in nigro-striatal slices. These observations suggest that MPTP N-oxide can directly cause the chemical depletion of striatal DA without modifying the characteristics of cortico-striate synaptic transmission.
Lau
Y S
YS
Department of Pharmacology, Creighton University, Omaha, Nebraska 68178-0224.
Fung
Y K
YK
Trobough
K L
KL
Cashman
J R
JR
Wilson
J A
JA
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D020267:MPTP Poisoning; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D003497:Cyclic N-Oxides; C065885:1-methyl-4-phenyl-1,2,3,6-(tetrahydropyridine)-N-oxide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine