Local perfusion of diazepam attenuates interictal and ictal events in the bicuculline model of epilepsy in rats

Purpose: We evaluated the efficacy of local perfusion of diazepam (DZP) in suppression of EEG spikes and behavioral seizures produced by bicuculline methiodide (BMI) applied to rat sensory motor cortex and hippocampus. Methods: Data were obtained from 37 rats implanted with EEG head plugs and perfusion cannulas. BMI 4 mM, 5 mu l was infused on neocortex through the epidural space in 23 rats. BMI 0.1 mM, 2 mu l was infused into the left hippocampus in 14 rats. Results: DZP 0.75-1.0 mg markedly reduced the spiking to a level of 9.9 +/- 15.8% of baseline for DZP as compared with 90.2 +/- 57.9% of baseline for vehicle-treated rats. DZP reduced spiking in a hippocampal BMI focus to 1.9 +/- 2.4% of baseline spiking, as compared with 98.0 +/- 95.6% of that in vehicle-treated animals. The amount of spread of solution was estimated with methylene blue (MB) injections. Ictal events also were attenuated. In most of the animals, systemic levels of DZP were unmeasurable and injection on the contralateral side did not reduce spiking. Conclusions: These findings suggest that focal application of antiepileptic drugs (AEDs) in brain may be a useful new avenue for therapy of intractable partial seizures.