Influence of ethanol on the pentylenetetrazol-induced kindling in rats

The effects of ethanol on the development of pentylenetetrazol (PTZ)-kindli ng as well as on fully PTZ-kindled convulsions in rats were investigated. E thanol (0.5, 1.0 and 1.5 g/kg i.p.) administered 15 min prior to each PTZ-i njection (35 mg/kg i.p.; 3 times/week) significantly inhibited the progress ive 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 a dministered 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 th ird 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. eth anol 10h prior to each PTZ-injection), significantly intensified the kindli ng development. In addition, studies with fully PTZ-kindled rats demonstrat ed that ethanol (0.1 to 1.5 g/kg i.p.), given Ij min prior or 2 min after P TZ, 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 repeate d administration of high doses with longer withdrawal periods leads to proc onvulsant actions, possible mediated via neuroadaptive changes in NMDA and/ or GABA(A) receptor-related mechanisms.