Fischer W, Kittner H
Institute of Pharmacology and Toxicology, University of Leipzig, Federal Republic of Germany.
J Neural Transm (Vienna). 1998;105(10-12):1129-42. doi: 10.1007/s007020050117.
The effects of ethanol on the development of pentylenetetrazol (PTZ)-kindling as well as on fully PTZ-kindled convulsions in rats were investigated. Ethanol (0.5, 1.0 and 1.5 g/kg i.p.) administered 15 min prior to each PTZ-injection (35 mg/kg i.p.; 3 times/week) significantly inhibited the progressive seizure development compared to saline-treated controls. For the higher doses of ethanol the kindling process was restricted to seizure stages of 1 or 2. Tolerance to this antiepileptogenic action did not occur even after 20 PTZ-stimulations. In a second series of experiments, 0.5 g/kg ethanol administered 10h before each PTZ-injection facilitated the rate of kindling development after 7 to 10 PTZ-injections, while the higher doses of ethanol did not modulate or even slightly reduced the seizure development. In a third test, intermittent administration of a high dose of ethanol (2 g/kg p.o.; twice daily for 6 days) before the kindling procedure (0.5 g/kg i.p. ethanol 10h prior to each PTZ-injection), significantly intensified the kindling development. In addition, studies with fully PTZ-kindled rats demonstrated that ethanol (0.1 to 1.5 g/kg i.p.), given 15 min prior or 2 min after PTZ, reduced the seizure severity in a dose-dependent manner. In conclusion, the present findings provide evidence for pronounced antiepileptogenic and anticonvulsant effects of ethanol after acute application, whereas repeated administration of high doses with longer withdrawal periods leads to proconvulsant actions, possible mediated via neuroadaptive changes in NMDA and/or GABA(A) receptor-related mechanisms.
研究了乙醇对大鼠戊四氮（PTZ）点燃模型的发展以及对完全PTZ点燃惊厥的影响。在每次PTZ注射（腹腔注射35mg/kg；每周3次）前15分钟腹腔注射乙醇（0.5、1.0和1.5g/kg），与生理盐水处理的对照组相比，显著抑制了癫痫发作的进展。对于较高剂量的乙醇，点燃过程局限于癫痫发作1或2期。即使经过20次PTZ刺激，对这种抗癫痫作用也未产生耐受性。在第二系列实验中，在每次PTZ注射前10小时腹腔注射0.5g/kg乙醇，在7至10次PTZ注射后促进了点燃发展速率，而较高剂量的乙醇未调节甚至略微降低了癫痫发作的发展。在第三个试验中，在点燃程序前（每次PTZ注射前10小时腹腔注射0.5g/kg乙醇）间歇性给予高剂量乙醇（口服2g/kg；每日两次，共6天），显著增强了点燃发展。此外，对完全PTZ点燃大鼠的研究表明，在PTZ前15分钟或后2分钟腹腔注射乙醇（0.1至1.5g/kg），以剂量依赖方式降低了癫痫发作的严重程度。总之，目前的研究结果为乙醇急性应用后明显的抗癫痫和抗惊厥作用提供了证据，而长时间撤药后重复给予高剂量乙醇会导致促惊厥作用，可能通过NMDA和/或GABA(A)受体相关机制的神经适应性变化介导。
