EFFECT OF ALCOHOL-WITHDRAWAL ON PENTYLENETETRAZOL-INDUCED SEIZURES IN RATS: A PROTECTIVE FUNCTION OF VITAMIN C

Abstract

Oxidative injury in the brain has been suggested as a common pathway of several neurologic diseases including epilepsy. Pentylenetetrazol (PTZ)-induced seizure is a proposed animal model of epilepsy. Further, animals have been shown to exhibit a PTZ-like stimulus after cessation of chronic alcohol treatment. The purpose of the present study is to further investigate the effect of alcohol withdrawal on acute PTZ-induced seizures, and the possible protective function of vitamin C. Seventy male rats were randomly allocated to control (saline-injected) and alcohol-treated groups. Animals were divided into seven groups, 10 animals each. Group 1, animals were injected with normal saline (0.9%), i.p., daily for two weeks. Other groups (Groups 2-7) were treated with ethyl alcohol (20% w/v) at a dose of 2 gm/kg body weight, i.p., daily for two weeks. Group 3, animals were pretreated with Vitamin C at a dose of 400 mg/kg body weight one hour before each alcohol injection. Group 4, animals were pretreated with Diazepam at a dose of 1 mg/kg body weight one hour before PTZ injection. Group 5, animals were pretreated with Vitamin C at a dose of 400 mg/kg body weight one hour before each alcohol injection; in addition, animals were pretreated once with Diazepam at a dose of 1 mg/kg body weight, i.p., one hour before PTZ injection. Group 6, animals were pretreated with Diazepam at a dose of 0.5 mg/kg body weight one hour before PTZ injection. Group 7, animals were pretreated with Vitamin C at a dose of 400 mg/kg body weight one hour before each alcohol injection; in addition, animals were pretreated once with Diazepam at a dose of 0.5 mg/kg body weight, 1.p., one hour before PTZ injection. All groups were treated acutely with PTZ at a dose of 30 mg/kg body weight, i.P., One day after the last injection of saline or alcohol. Seizures were evaluated using the modified Racine's scale. The undetected effects of the subconvulsive dose of PIZ (30 mg/kg) was clearly observed in alcohol-withdrawing animals Pretreatment with Vitamin C alone could not prevent PIZ-induced seizures. In contrast, Diazepam (1 mg/kg) could decrease seizures score. This protective effect of diazepam has dissipated upon dose reduction (DZP, 0.5 mg/kg). However, the combined effects of Diazepam (0.5 mg/kg) and Vitamin C (400 mg/kg) proved to be effective in suppressing the convulsant effect of PTZ in alcohol-withdrawing animals. It is concluded that alcohol withdrawal enhanced the sensitivity of animals to the acute convulsant effects of PTZ. Vitamin C could not block seizure activity, however, it enhanced the anticonvulsant effects of diazepam.