Periodic transmeningeal administration of
muscimol into the neocortical epileptogenic zone via a subdurally implanted device has been proposed for the treatment of intractable focal neocortical
epilepsy. It is unknown whether such
muscimol applications induce tolerance. The purpose of this study was to determine whether daily transmeningeal (epidural)
muscimol applications into the rat parietal cortex induce tolerance to the
antiepileptic effect of this
drug. Rats were chronically implanted with an epidural cup and adjacent epidural EEG
electrodes over the right parietal cortex. After recovery 1.0 mM
muscimol was delivered into the implanted cortical area through the cup while the animal behaved freely, once per day for 4 consecutive days in each week, with each delivery followed within 3 min by the delivery of a seizure-inducing concentration of
acetylcholine (Ach) into the same area. The study lasted for 3 weeks. In each week, one day was used to test the epileptogenicity of the examined cortical site by replacing
muscimol with saline prior to Ach delivery. The duration of Ach-induced EEG
seizures was measured in each experimental session to assess the
antiepileptic efficacy of
muscimol, while the rat's behavior was also monitored. The daily epidural
muscimol pretreatments prevented Ach-induced EEG and behavioral
seizures in all rats. This
antiepileptic action did not diminish over time and was maintained throughout the 3-week test period. When
muscimol was replaced with saline, the subsequent Ach administrations induced EEG and behavioral
seizures. These results suggest that periodic transmeningeal administrations of a relatively low concentration of
muscimol into the neocortex over three weeks do not induce tolerance to the localized
antiepileptic effects of this
drug.