SL 82.0715, AN NMDA ANTAGONIST ACTING AT THE POLYAMINE SITE, DOES NOT INDUCE NEUROTOXIC EFFECTS ON RAT CORTICAL-NEURONS

被引:46
作者
DUVAL, D
ROOME, N
GAUFFENY, C
NOWICKI, JP
SCATTON, B
机构
[1] SYNTHELABO LERS,RECH,DEPT BIOL,LERS,31 AVE PAUL VAILLANT COUTURIER,F-92220 BAGNEUX,FRANCE
[2] DEPT DRUG SAFETY,GARGENVILLE,FRANCE
关键词
NEUROTOXICITY; N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST; POLYAMINE SITE;
D O I
10.1016/0304-3940(92)90402-S
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In the present study, we have examined by light and electron microscopy whether SL 82.0715, a polyamine site-directed N-methyl-D-aspartate (NMDA) antagonist, causes pathological changes in cerebrocortical neurons similar to those observed with NMDA receptor channel blockers in the rat brain. Dizocilpine (1, 2 and 5 mg.kg-1, s.c.) induced a dose-dependent vacuolization of the neuronal cytoplasm in specific neurons of the retrosplenial and posterior cingulate cortices (layers III and IV) even at the lowest dose studied, at 6 h post-injection. In contrast, SL 82.0715 (10 and 30 mg.kg-1 i.p., 6 h post-injection) did not induce such morphological alterations. These results indicate that NMDA receptor blockade is not necessarily associated with alterations of cortical neuronal morphology.
引用
收藏
页码:193 / 197
页数:5
相关论文
共 23 条
[1]   N-METHYL-D-ASPARTATE ANTAGONISTS - READY FOR CLINICAL-TRIAL IN BRAIN ISCHEMIA [J].
ALBERS, GW ;
GOLDBERG, MP ;
CHOI, DW .
ANNALS OF NEUROLOGY, 1989, 25 (04) :398-403
[2]  
ALLEN HL, 1990, SCIENCE, V247, P221, DOI 10.1126/science.2403696
[3]  
BALSTER RL, 1987, PSYCHOPHARMACOLOGY 3, P1573
[4]  
CARTER C, 1988, J PHARMACOL EXP THER, V247, P1222
[5]  
CARTER CJ, 1990, J PHARMACOL EXP THER, V253, P475
[6]   KETAMINE EFFECTS ON LOCAL CEREBRAL BLOOD-FLOW AND METABOLISM IN THE RAT [J].
CAVAZZUTI, M ;
PORRO, CA ;
BIRAL, GP ;
BENASSI, C ;
BARBIERI, GC .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1987, 7 (06) :806-811
[7]   THE ROLE OF EXCITATORY AMINO-ACIDS AND NMDA RECEPTORS IN TRAUMATIC BRAIN INJURY [J].
FADEN, AI ;
DEMEDIUK, P ;
PANTER, SS ;
VINK, R .
SCIENCE, 1989, 244 (4906) :798-800
[8]  
FRANCE CP, 1991, J PHARMACOL EXP THER, V257, P727
[9]   NEUROPROTECTIVE EFFECT OF MK-801 AND U-50488H AFTER CONTUSIVE SPINAL-CORD INJURY [J].
GOMEZPINILLA, F ;
TRAM, H ;
COTMAN, CW ;
NIETOSAMPEDRO, M .
EXPERIMENTAL NEUROLOGY, 1989, 104 (02) :118-124
[10]   THE PHARMACOTHERAPY OF FOCAL CORTICAL ISCHEMIA IN THE MOUSE [J].
GOTTI, B ;
BENAVIDES, J ;
MACKENZIE, ET ;
SCATTON, B .
BRAIN RESEARCH, 1990, 522 (02) :290-307