Objective  

To investigate changes in free benzodiazepine receptor density in response to repeated, long-term administration of diazepam in epilepsy, we assessed¹²⁵I-iomazenil (¹²⁵I-IMZ) binding in a mouse model.

Methods  

El mice were divided into two groups of 12 mice each which received either no diazepam (EI(D[-]) group) or 2 mg/kg of diazepam per week (EI(D[+]) group). Nine ddY mice were used as a control. Once each week from the age of 5 to 19 weeks, the El mice received stimulation to produce epileptic seizures 20 minutes after receiving intraperitoneal injections. At 20 weeks of age, a total dose of 0.37 MBq of¹²⁵I-IMZ was injected in all mice and their brains were rapidly removed 3 hours later. The incidence of epileptic seizures at the age of 19 weeks and the autoradiograms of the brain were compared.

Results  

The incidence of epileptic seizures in response to weekly stimulation was significantly lower in the E1(D[+]) group than in the E1(D[-]) group (p < 0.001). The percent injected doses of¹²⁵I-IMZ per gram of tissue in the cortex, hippocampus and amygdala were significantly lower in the E1(D[+]) group than in the E1(D[-]) group (p < 0.05).

Conclusion  

The results suggest that diazepam binds competitively to¹²⁵I-IMZ as an agonist to free benzodiazepine receptor sites in the cortex, hippocampus and amygdala and shows anticonvulsant effect in El mice.