Ibogaine alters synaptosomal and glial glutamate release and uptake

被引:11
作者
Leal, MB
Emanuelli, T
Porciúncula, LD
Souza, DO
Elisabetsky, E
机构
[1] Univ Fed Rio Grande Sul, ICBS, Pos Grad Ciencias Biol, BR-90041970 Porto Alegre, RS, Brazil
[2] Univ Fed Rio Grande Sul, ICBS, Dept Farmacol, BR-90041970 Porto Alegre, RS, Brazil
[3] Univ Fed Santa Maria, CCR, Dept Tecnol & Ciencia Alimentos, BR-97119900 Santa Maria, RS, Brazil
关键词
astrocyte; glutamate; ibogaine; mice; rats; release; synaptosomes; uptake;
D O I
10.1097/00001756-200102120-00017
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Ibogaine has aroused expectations as a potentially innovative medication for drug addiction. It has been proposed that antagonism of the NMDA receptor by ibogaine may be one of the mechanisms underlying its antiaddictive properties; glutamate has also been implicated in ibogaine-induced neurotoxicity. We here report the effects of ibogaine on [H-3]glutamate release and uptake in cortical and cerebellar synaptosomes, as well as in cortical astrocyte cultures, from mice and rats. Ibogaine (2-1000 muM) had no effects on glutamate uptake or release by rat synaptosomes. However, ibogaine (500-1000 muM) significantly inhibited the glutamate:uptake and stimulated the release of glutamate by cortical (but not cerebellar) synaptosomes of mice. In addition,ibogaine (1000 muM) nearly abolished glutamate uptake by cortical astrocyte cultures from rats and mice. The data provide direct evidence of glutamate involvement in ibogaine-induced neurotoxicity. NeuroReport 12:263-267 (C) 2001 Lippincott Williams & Wilkins.
引用
收藏
页码:263 / 267
页数:5
相关论文
共 26 条
[1]  
Alper KR, 1999, AM J ADDICTION, V8, P234
[2]  
Anderson CM, 2000, GLIA, V32, P1
[3]   A RAPID PERCOLL GRADIENT PROCEDURE FOR ISOLATION OF SYNAPTOSOMES DIRECTLY FROM AN S-1 FRACTION - HOMOGENEITY AND MORPHOLOGY OF SUBCELLULAR-FRACTIONS [J].
DUNKLEY, PR ;
HEATH, JW ;
HARRISON, SM ;
JARVIE, PE ;
GLENFIELD, PJ ;
ROSTAS, JAP .
BRAIN RESEARCH, 1988, 441 (1-2) :59-71
[4]   Cellular distribution and kinetic properties of high-affinity glutamate transporters [J].
Gegelashvili, G ;
Schousboe, A .
BRAIN RESEARCH BULLETIN, 1998, 45 (03) :233-238
[5]   Mechanisms of antiaddictive actions of ibogaine [J].
Glick, SD ;
Maisonneuve, IM .
NEUROCHEMISTRY OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES, 1998, 844 :214-226
[6]  
HOUGH LB, 1996, LIFE SCI, V58, P119
[7]  
LIPTON SA, 1994, NEW ENGL J MED, V330, P613
[8]  
LOWRY OH, 1951, J BIOL CHEM, V193, P265
[9]   IBOGAINE POSSESSES A SELECTIVE AFFINITY FOR SIGMA(2) RECEPTORS [J].
MACH, RH ;
SMITH, CR ;
CHILDERS, SR .
LIFE SCIENCES, 1995, 57 (04) :PL57-PL62
[10]   Medication development of ibogaine as a pharmacotherapy for drug dependence [J].
Mash, DC ;
Kovera, CA ;
Buck, BE ;
Norenberg, MD ;
Shapshak, P ;
Hearn, WL ;
Sanchez-Ramos, J .
NEUROCHEMISTRY OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES, 1998, 844 :274-292