Effects of diazepam on 125I-iomazenil-benzodiazepine receptor binding and epileptic seizures in the El mouse

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

El mice were divided into two groups of 12 mice each which received either no diazepam (E1(D[-]) group) or 2 mg/kg of diazepam per week (El(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 of 125I-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.

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 of 125I-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).

The results suggest that diazepam binds competitively to 125I-IMZ as an agonist to free benzodiazepine receptor sites in the cortex, hippocampus and amygdala and shows anticonvulsant effect in E1 mice.