The Effect of Ethanol on the Efficacy of Valproic Acid in Mice

Background and Ethanol is known as anticonvulsant and proconvulsant but sometimes has no effect on seizure. There is no report about the role of ethanol on the anticonvulsant effect of Valproic acid (VPA). In this study, we explore the effect of ethanol on the anticonvulsant effect of VPA. Methods and Materials: In this experimental study, eight groups of mice (25-30 gr) were injected pentylenetetrazol (PTZ) (37 mg/kg; ip) every other day (3 times a week). Groups receiving ethanol (0.5 and 1 g/kg; 7 and 21 continuous days; everyday; ip), PTZ was injected 30 minutes after ethanol. In Valproic acid+ethanol, Valproic acid (100 mg/kg) was injected 5 minutes before ethanol (1 g/kg). Immediately after PTZ injection, seizure stages were recorded for 20 min. Seizure stage-4 duration (S4D), seizure stage-4 latency (S4L) and seizure stage 1 latency (S1L) were recorded from each mouse after PTZ injection, and data were compared with control groups. The basis of all decisions was a significant level of P<0.05. Data analysis was done in Statistica 5.5. Pretreatment of animals with ethanol (1 g/kg for 7 days) decreased cumulative (c) S4D (%31.8 PTZ+Saline); and with ethanol (1 g/kg for 21 days) decreased cS4D (%48.3 PTZ+Saline) (P<0.001), but increased cS4L (%112.6 PTZ+Saline) and cSL (%116.8 PTZ+Saline) significantly (P<0.001). Pretreatment of animals with VPA (100 mg/kg) significantly decreased cumulative (c) S4D (%39 PTZ+Saline) (P<0.001), and significantly increased cS4L (%216.8 PTZ+Saline) and cS1L (%149 PTZ+Saline) (P<0.001). Intraperitoneal injection of VPA+ethanol significantly decreased cS4D (%56.1 relative to PTZ+VPA and %46.1 relative to PTZ+Eth 1 (7)) (P<0.001); it also increased cS4L (%233.9 relative to PTZ+VPA and %450 relative to PTZ+Eth1 (7)) (P<0.001), but had no effect on cS1L as compared to VPA and ethanol (1 g/kg; 7 days). The results indicated that ethanol (1 g/kg) functions not only as an anticonvulsant but its simultaneous injection (7 continuous days) also enhances the anticonvulsant effects of valproic acid.