Effects of intravenous administration of propofol and midazolam on pentylenetetrazole kindled seizures in rats

Abstract

To date, studies examining the proconvulsants or anticonvulsants in chronic epileptic models in rat are rare. Propofol has conflicting reports regarding the pro- or anti-convulsant effects on chronic seizures. Midazolam is considered another anesthetic option that used in combination with propofol and has documented anticonvulsant properties. The present study was undertaken to examine the effects of intravenous administration of various doses of propofol, in comparison to midazolam, on seizures activity in chronically epileptic rats, using PTZ seizures kindled model. Kindling in control and experimental rats was induced by intraperitoneal sub - convulsive dose of PTZ (35 mg/kg) every alternate day. After each injection of PTZ, rats were monitored for 30 minutes for behavioral seizures occurrence. Seizure scores were rated according to Racin scale. Once kindled, animals were treated with different doses of midazolam or propofol prior to PTZ challenge and were subsequently observed. The present study showed that, propofol or midazolam intravenous administration suppressed PTZ seizures in kindled rats and led to a significant, dose dependent decrease of behavioral seizures score and increased the percent inhibition of PTZ kindled seizures stage. The ED50 of propofol for percent inhibition of PTZ kindled seizures stage was 5.36 mg/kg, whereas the ED50 of midazolam was 1.85 mg/kg, suggesting that the anticonvulsant effects of midazolam against PTZ kindled seizures are more profound. In conclusion, the current study showed that propofol protected against PTZ kindled seizures and provided further evidence for its anticonvulsant effects reported in other chronic animal seizures, namely amygdala-kindled convulsions in rats.