PRETREATMENT WITH NIMODIPINE PREVENTS MPTP-INDUCED NEUROTOXICITY AT THE NIGRAL, BUT NOT AT THE STRIATAL LEVEL IN MICE

被引:72
作者
KUPSCH, A
GERLACH, M
PUPETER, SC
SAUTTER, J
DIRR, A
ARNOLD, G
OPITZ, W
PRZUNTEK, H
RIEDERER, P
OERTEL, WH
机构
[1] UNIV MUNICH,INST PHYSIOL,W-8000 MUNICH,GERMANY
[2] DEPT PSYCHIAT,WURZBURG,GERMANY
[3] RUHR UNIV BOCHUM,DEPT NEUROL,W-4630 BOCHUM,GERMANY
[4] TROPONWERKE GMBH & CO KG,COLOGNE,GERMANY
关键词
NIMODIPINE; MPTP; CALCIUM; CHANNEL BLOCKER; MOUSE; PARKINSONS DISEASE; NEUROTOXICITY; TYROSINE HYDROXYLASE; DOPAMINE;
D O I
10.1097/00001756-199503000-00009
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:621 / 625
页数:5
相关论文
共 23 条
[1]  
BAR PR, 1990, J NEUR TR S, V31, P55
[2]   RILUZOLE AND EXPERIMENTAL PARKINSONISM - PARTIAL ANTAGONISM OF MPP(+)-INDUCED INCREASE IN STRIATAL EXTRACELLULAR DOPAMINE IN RATS IN-VIVO [J].
BOIREAU, A ;
MIQUET, JM ;
DUBEDAT, P ;
MEUNIER, M ;
DOBLE, A .
NEUROREPORT, 1994, 5 (16) :2157-2160
[3]   ROLE OF CYCLING OR FLUXES OF EXTRACELLULAR CALCIUM-ION ON 1-METHYL-4-PENYLPYRIDINE (MPP+) INDUCED SUSTAINED EXOCYTOSIS OF ENDOGENOUS STRIATAL DOPAMINE INVIVO [J].
CHIUEH, CC ;
MIYAKE, H ;
HUANG, SJ ;
PENG, MT .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1990, 183 (03) :1069-1070
[4]  
CHIUEH CC, 1991, POSTERS NEUROSCI, V1, P37
[5]   LONG-TERM EFFECT OF MPTP IN THE MOUSE-BRAIN IN RELATION TO AGING - NEUROCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS [J].
DATE, I ;
FELTEN, DL ;
FELTEN, SY .
BRAIN RESEARCH, 1990, 519 (1-2) :266-276
[6]  
DEJONGE MC, 1993, CLIN NEUROPHARMAC S1, V16, P25
[7]  
DIPAOLO T, 1986, BRAIN RES, V379, P286
[8]   DIFFERENT EFFECTS OF THE CALCIUM-ANTAGONISTS NIMODIPINE AND FLUNARIZINE ON DOPAMINE METABOLISM IN THE RAT-BRAIN [J].
FADDA, F ;
GESSA, GL ;
MOSCA, E ;
STEFANINI, E .
JOURNAL OF NEURAL TRANSMISSION, 1989, 75 (03) :195-200
[9]   COMPARISON AMONG THE EFFECTS OF NIFEDIPINE, NIMODIPINE AND NISOLDIPINE ON THE BRAIN BIOGENIC-AMINES OF NORMAL OR HALOPERIDOL TREATED RATS [J].
GAGGI, R ;
CONT, R ;
GIANNI, AM .
GENERAL PHARMACOLOGY, 1993, 24 (05) :1091-1096
[10]  
GERLACH M, 1993, ARZNEIMITTELFORSCH, V43-1, P413