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.