Abstracts

Pharmacological inhibition and high-frequency stimulation (HFS) of the substantia nigra pars reticulata (SNr) have been shown to suppress seizures in different animal models. The aim of the present study was to determine the most effective stimulation parameters to interrupt spike-and-wave discharges (SWD) by HFS of the SNr, in a genetic model of absence epilepsy in the rat (GAERS). Nineteen male GAERS were stereotaxically implanted bilaterally with bipolar electrodes in the SNr and with monopolar epidural electrodes. After one week of recovery, the effects of either (i) isolated 5-s or (ii) continous bipolar HFS were investigated. For each conditions, the effects of changes in the following parameters were determined: uni- versus bilateral, mono- versus biphasic mode, frequencies and pulse widths. Bilateral isolated HFS with a frequency of 130Hz and a pulse width of 60us were the most effective to interrupt SWD at a threshold significantly different from intensity inducing motor side effects. However, repetition of such stimulations on 3 (+0,25) (monophasic) or 6 (+1,33) (biphasic) consecutive seizures, was found to become ineffective. At antiepileptic thresholds, continuous bilateral HFS (130Hz, 60us) did not suppress seizures. However when intensity was progressively increased by 5uA steps after each seizure, suppression of SWD could be obtained. These results show that bilateral and biphasic isolated stimulation of SNr with a frequency of 130Hz and a pulse width of 60us interrupt absence seizures without motor side effects. Repetition of such stimulation leads to a loss of the antiepileptic effects. Continuous chronic stimulation has no significant effect. These results suggest that continuous stimulation protocols need to be further evaluated. (Supported by a ENS Fellowship, French Ministry of Research and Fondation pour la Recherche sur le Cerveau.)