PENTYLENETETRAZOL-INDUCED KINDLING IN RATS - EFFECT OF GABA FUNCTION INHIBITORS
PENTYLENETETRAZOL-INDUCED KINDLING IN RATS - EFFECT OF GABA FUNCTION INHIBITORS
复制标题
DOI：
10.1016/0091-3057(91)90562-g
复制
发表时间：
1991-10-01
影响因子：
3.6
通讯作者：
GIORGI, O
中科院分区：
文献类型：
--
作者：
CORDA, MG;ORLANDI, M;GIORGI, O
反复给予亚惊厥剂量的戊四唑（PTZ）产生了对该化合物作用的进行性致敏作用（即，化学点燃）。使用两种不同的给药方案观察到PTZ诱导点燃的时间过程非常相似：1）每天一次注射（30 mg/kg，IP），和2）每两天一次注射（30 mg/kg，IP）。当这些治疗方案连续使用8周时，超过80%的大鼠在治疗结束时出现惊厥。相比之下，如果PTZ以15 mg/kg的剂量每天两次IP给药，则只有20%的大鼠致敏。在慢性治疗完成一年后，对PTZ惊厥效应的敏感性增加仍然存在。此外，PTZ点燃大鼠表现出对中枢GABA能功能的不同抑制剂诱导的惊厥的敏感性增强，所述抑制剂例如氯离子通道阻断剂印防己毒素、苯二氮卓受体配体FG 7142和Ro 15-4513以及GABA合成抑制剂异烟肼。相反，甘氨酸受体拮抗剂士的宁的惊厥作用的敏感性是不变的，反复PTZ管理。这表明，点燃所产生的PTZ可能与持续减少的抑制功能的GABA能系统在大脑中。
The repeated administration of subconvulsant doses of pentylenetetrazol (PTZ) produced a progressive sensitization to the effects of this compound (i.e., chemical kindling) in the rat. A very similar time-course for PTZ-induced kindling was observed using two different treatment schedules: 1) one injection every day (30 mg/kg, IP), and 2) one injection (30 mg/kg, IP) every second day. When these treatment schedules were used for eight consecutive weeks, more than 80% of the rats displayed convulsions by the end of treatment. In contrast, only 20% of the rats were sensitized if PTZ was administered twice daily at the dose of 15 mg/kg, IP. The increased sensitivity to the convulsant effect of PTZ was still present one year after completion of the chronic treatment. Moreover, rats kindled with PTZ showed an enhanced susceptibility to convulsions induced by different inhibitors of central GABAergic function, such as the chloride channel blocker picrotoxin, the benzodiazepine receptor ligands FG 7142 and Ro 15-4513, and the inhibitor of GABA synthesis isoniazid. In contrast, the sensitivity to the convulsant action of the glycine receptor antagonist strychnine was unchanged by repeated PTZ administration. It is suggested that kindling produced by PTZ may be associated with a persistent reduction in the inhibitory function of the GABAergic system in the brain.