Pretreatment with nimodipine prevents MPTP-induced neurotoxicity at the nigral, but not at the striatal level in mice.
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.
Kupsch
A
A
Klinikum Grosshadern, Department of Neurology, Ludwig-Maximilians-University, München, Germany.
Gerlach
M
M
Pupeter
S C
SC
Sautter
J
J
Dirr
A
A
Arnold
G
G
Opitz
W
W
Przuntek
H
H
Riederer
P
P
Oertel
W H
WH
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
D015306:Biogenic Monoamines; D009553:Nimodipine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine