Hypobaric epileptiform reaction in Krushinsky-Molodkina rats as a new experimental model for testing anticonvulsants

Abstract

Previously it was found that Krushinsky-Molodkina (KM) rats responded to a sharp decline in atmospheric pressure with a hypobaric epileptiform reaction (HER), motor excitation resulting in tonic-clonic seizure. The aim of the study was to confirm that HER was suitable for testing anticonvulsants in KM rats. Methods. Carbamazepine and sodium valproate were administered to rats intraperitoneally at doses of 30 mg/kg and 200 mg/kg, respectively. For modeling HER, rats were placed in an individual chamber equipped with an altimeter and “elevated” to a simulated altitude of 5,000 m at a speed of 50 m/sec using a vacuum pump. In the process of elevation, rats developed HER. The HER parameters were evaluated before and after the anticonvulsant administration. Results. In 1—1.5 hours after administration of the anticonvulsants, carbamazepine and sodium valproate, HER was observed only in 30% and 40% of rats. Furthermore, the “altitude” in meters of the motor excitation onset was increased whereas the seizure severity in scores was decreased. The rest of the rats had no signs of HER. The protective effect of carbamazepine disappeared at 24 hours after the injection while the protective effect of sodium valproate remained in 50% of rats. Conclusion. Using a model of reflex epilepsy induced by vacuum decompression, carbamazepine and sodium valproate were shown to be equally effective in 1—1.5 hours after their administration; however, the protective effect of sodium valproate stayed longer than that of carbamazepine. HER in KM rats can be used as an experimental model for testing anticonvulsants.