title: Pretreatment with nimodipine prevents MPTP-induced neurotoxicity at the nigral, but not at the striatal level in mice.
abstract: The present study assessed the effects of pretreatment with the calcium-L-type channel blocker nimodipine on biochemical and histological parameters of systemic MPTP-induced (2 x 40 mg kg-1 body weight subcutaneously, 16 h apart), dopaminergic neurotoxicity in black C57BL/6 mice. Continuous administration of nimodipine via subcutaneously implanted pellets (10 mg), starting 7 days before administration of MPTP, did not antagonize the striatal MPTP-induced dopamine depletion (caudate-putamen: 80% of control; nucleus accumbens; 25% of control), but almost completely prevented the MPTP-induced tyrosine hydroxylase immunoreactive-cell loss in the substantia nigra (20% of control) 7 days after administration of MPTP. This data suggests that pretreatment with nimodipine--during the observation period of 7 days--protects against MPTP-induced neurotoxicity in mice at the nigral ('cell body'), but not at the synaptic striatal level.
authors.affiliation: Klinikum Grosshadern, Department of Neurology, Ludwig-Maximilians-University, München, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kupsch
authors.forename: M
authors.initials: M
authors.lastname: Gerlach
authors.forename: S C
authors.initials: SC
authors.lastname: Pupeter
authors.forename: J
authors.initials: J
authors.lastname: Sautter
authors.forename: A
authors.initials: A
authors.lastname: Dirr
authors.forename: G
authors.initials: G
authors.lastname: Arnold
authors.forename: W
authors.initials: W
authors.lastname: Opitz
authors.forename: H
authors.initials: H
authors.lastname: Przuntek
authors.forename: P
authors.initials: P
authors.lastname: Riederer
authors.forename: W H
authors.initials: WH
authors.lastname: Oertel
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D016014:Linear Models; D051379:Mice; D008810:Mice, Inbred C57BL; D009553:Nimodipine / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015306:Biogenic Monoamines; D009553:Nimodipine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine