2,3-BUTANEDIONE MONOXIME PROTECTS MICE AGAINST THE CONVULSANT EFFECT OF PICROTOXIN BY FACILITATING GABA-ACTIVATED CURRENTS

被引:6
作者
BRIGHTMAN, T
YE, JH
ORTIZJIMENEZ, E
FLYNN, EJ
WU, WH
MCARDLE, J
机构
[1] UNIV MED & DENT NEW JERSEY, NEW JERSEY MED SCH, DEPT PHARMACOL & TOXICOL, NEWARK, NJ 07103 USA
[2] UNIV MED & DENT NEW JERSEY, NEW JERSEY MED SCH, DEPT ANESTHESIOL, NEWARK, NJ 07103 USA
关键词
PICROTOXIN; CONVULSION; 2,3-BUTANEDIONE MONOXIME; GAMMA-AMINOBUTYRIC ACID; ANTICONVULSANT; WHOLE CELL CURRENT IN RESPONSE TO GABA; 2,3-BUTANEDIONE;
D O I
10.1016/0006-8993(95)00175-P
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
While adult mice receiving picrotoxin (PTX) alone responded with clonic and tonic-clonic seizures, this response was greatly suppressed for mice simultaneously injected with 2,3-butanedione monoxime (BDM). For example, 60% and 10% of the mice convulsed when injected (i.p.) with 3.0 mg/kg PTX alone or PTX plus 205 mg/kg of BDM, respectively. In contrast, a non-oxime analogue of BDM, 2,3-butanedione (BTD), did not have this anticonvulsant effect. In order to explore the basis for the anticonvulsant effect of BDM, we recorded GABA-activated currents (I-GABA) of frontal cortical as well as ventromedial hypothalamic neurons before, during and after exposure to this oxime. BDM had a biphasic effect on I-GABA. That is, high concentrations (100 mu M-40 mM) decreased and lower concentrations (0.01 mu M-0.001 mu M) potentiated I-GABA; these effects of BDM reversed upon washout of the oxime. In contrast, BTD had no effect on I-GABA. Finally, when 0.001 mu M BDM, 10-30 mu M PTX and GABA were co-applied the inhibitory effect of the toxin on I-GABA was markedly suppressed. These data suggest that the anticonvulsant effect of oximes involves facilitation of the inhibitory action of GABA.
引用
收藏
页码:110 / 116
页数:7
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