Neuroprotective effects of rotigotine in the acute MPTP-lesioned mouse model of Parkinson's disease.
Dopamine agonists used to manage Parkinsonian motor symptoms have been suggested to be neuroprotective. The study was designed to assess the neuroprotective potential of the D(3)/D(2)/D(1) dopamine receptor agonist rotigotine in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned (MPTP) mouse model of Parkinson's disease by measuring mesencephalic degenerating neurons using FluoroJade staining and the remaining dopaminergic nerve endings in the striatum using dopamine transporter binding. Continuous administration of rotigotine at a dose of 3mg/kg significantly attenuated MPTP-induced acute cell degeneration in the FluoroJade-staining paradigm. Rotigotine (0.3-3mg/kg) partially protected dopamine nerve endings from MPTP-induced degeneration in a dose-dependent manner. These data suggest that rotigotine, at the doses employed, significantly protected dopamine neurons from degeneration in an acute mouse model of MPTP intoxication.
Scheller
Dieter
D
SCHWARZ BIOSCIENCES GmbH, Alfred-Nobel Strasse 10, Monheim, Germany. dieter.scheller@schwarzpharma.com
Stichel-Gunkel
Christine
C
Lübbert
Hermann
H
Porras
Gregory
G
Ravenscroft
Paula
P
Hill
Michael
M
Bezard
Erwan
E
D000208:Acute Disease; D000279:Administration, Cutaneous; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000188:drug therapy / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000517:prevention & control*; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D018491:Dopamine Agonists; D007457:Iodine Radioisotopes; D018696:Neuroprotective Agents; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine