Reduction of dopamine uptake and cocaine binding in mouse striatum by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) (daily injections of 8 mg/kg for 5 days via tail vein) reduced [3H]dopamine uptake in striatal synaptosomes by 63% and reduced [3H]cocaine binding to striatal membranes by 61%. [3H]Cocaine binding was not affected in olfactory tubercle, suggesting a selective effect of NMPTP on the nigro-striatal but not on the mesolimbic dopaminergic system. The destruction of dopamine terminals in the striatum did not alter (up-regulate) [3H]spiroperidol binding. The results suggest that NMPTP causes a degenerative destruction of the striatal dopamine pathway and that NMPTP may be useful in developing a rodent model of Parkinson's disease.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003042:Cocaine / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003864:Depression, Chemical; D004298:Dopamine / Q000378:metabolism*; D006892:Hydroxydopamines / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011725:Pyridines / Q000494:pharmacology*; D013134:Spiperone / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism
D006892:Hydroxydopamines; D011725:Pyridines; D013134:Spiperone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003042:Cocaine; D004298:Dopamine