Inhibitory effects of midazolam on amygdala kindling in rats and maximal electroshock seizure in mice / 中国组织工程研究

ABSTRACT

BACKGROUND: Typically antiepileptic drugs, such as phenobarbital, fenitoina sodica and diazepam, can inhibit amygdala kindling effect in rats. However, whether midazolam has the same effect is still unclear.OBJECTIVE: To investigate the inhibitory effect of midazolam on amygdala kindling onset in rats and maximal electroshock seizure (MES) in mice and effeots of antiepileptic drugs.DESIGN: This study was divided into three subexperiments, including the effects of midazolam on amygdala kindling onset, independent activities and incidence convulsion. All the three subexperiments were completely randomized,infra-group control or self-control studies.SETTING: Medical College of Qingdao University.MATERIALS: The experiment was carried out in the Comprehensive Experimental Room, Affiliated Hospital of Medical College of Qingdao University from August 2004 to March 2005. Nine Wistar rats weighing (250±10) g and 120 Kunming mice weighing (20±5) g and either gender were provided by Animal Center of Qingdao Institute of Drug Control.Midazolam (5 g/L) was provided by Xuzhou Enhua Drugs Co., Ltd. (batch number: 20030706).METHODS: ① Establishment of amygdala kindling models: Nine kindled rats were randomly selected and intraperitoneally injected with 0.25, 0.5 and 1 mg/kg midazolam, respectively. Quadri-pathway biological signal processing system (SMUP-PC) was used to measure discharge duration (ADD) and Racine's stage. ② Sixty mice were randomly divided into 5 groups, including saline group, 40 mg/kg phenobarbital group, 0.5, 1.0 and 1.5 mg/kg midazolam groups with 12 mice in each group. And then, numbers of activities in a unit time (times per 5 minutes) were determined by XZC-4A mini-animals independent activity instrument. ③ MES models were established to calculate incidence of convulsion.MATN OUTCOME MEASURES: Effects of midazolam on ADD, Racine's stage, numbers of independent activities and incidence of convulsion.RESULTS: All the 9 rats and the 120 mice were involved in the final analysis. ① Effect of midazolam on amygdala kindling onset: After intraperitoneal injection of 0.5 and 1.0 mg/kg midazolam, ADD and Racine's stage were obviously lower than those before administration (P ＜ 0.05-0.01). After intraperitoneal injection of 0.25 mg/kg midazolam, ADD was obviously lower than that before administration (P ＜ 0.05), but there was no significant difference in Racine's stage. ②Effect of midazolam on independent activities of mice: Numbers of independent activities were lower in the phenobarbital group and 0.5, 1.0 and 1.5 mg/kg midazolam groups than those in the saline group (P ＜ 0.01), while numbers of independent activities were higher in 0.5 mg/kg midazolam group than those in the phenobarbital group (P ＜ 0.05). ③Effect of midazolam on maximal electroshock seizure: Incidence of convulsion was lower in the phenobarbital group and 0.5, 1.0 and 1.5 mg/kg midazolam groups than that in the saline group (P ＜ 0.05-0.01), while Incidence of convulsion was higher in 0.5 mg/kg midazolam group than that in the phenobarbital group (P＜ 0.05).CONCLUSION: Midazolam can significantly inhibit amygdala kindling onset, reduce numbers of independent activities,and antagonist MES in mice.