DEVELOPMENT AND REVERSAL OF CONTINGENT INEFFICACY AND TOLERANCE TO THE ANTICONVULSANT EFFECTS OF CARBAMAZEPINE

被引:40
作者
WEISS, SRB [1 ]
POST, RM [1 ]
机构
[1] NIMH,BIOL PSYCHIAT BRANCH,ROOM 3N212,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892
关键词
ANTICONVULSANT; CARBAMAZEPINE; KINDLING; SEIZURES; NEUROLOGIC MODELS;
D O I
10.1111/j.1528-1157.1991.tb05626.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The relationship of the timing of drug administration to anticonvulsant efficacy against amygdalakindled seizures was studied. During kindling development, rats received carbamazepine (CBZ, 15 mg/kg) before (CBZ-before) or after each amygdala stimulation (CBZ-after). After kindling to full seizures, when all animals were given CBZ before the stimulation, only the CBZ-after group showed a good anticonvulsant response. The rats that had received CBZ before (during development of kindled seizures) remained unresponsive to CBZ treatment (contingent inefficacy). When drug-naive or CBZ-after animals repeatedly received CBZ before electrical stimulation, they developed tolerance to its anticonvulsant effects (contingent tolerance). The tolerance could be reversed by a period of treatment with CBZ-after or by kindling the animal drug-free, but not by CBZ administration alone or by time off from both drug and seizures. These findings suggest that inefficacy and tolerance to CBZ may be affected by the temporal contingencies of drug administration and that responsiveness can be reinstated by altering these contingencies.
引用
收藏
页码:140 / 145
页数:6
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