Inhibitory effects of midazolam on amygdala kindling in rats and maximal electroshock seizure in mice

Xuejuan ZHANG; Li SONG; Wang YUE; Ran LIU

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.