Lack of robust anticonvulsant effects of muscimol microinfusions in the anterior substantia nigra of kindled rats

Abstract

The substantia nigra pars reticulata is thought to control the spread of seizures in various seizure models. Potentiation of γ-aminobutyrate (GABA)-mediated transmission in this region by intranigral administration of drugs such as muscimol has been shown to inhibit seizure propagation in such models, including the kindling model of epilepsy. More recent studies have shown that the effects on seizures are site-specific within the substantia nigra pars reticulata. Using flurothyl to induce clonic seizures, it was reported that bilateral microinfusions of muscimol into the anterior substantia nigra pars reticulata were anticonvulsant, while similar infusions into the posterior pars reticulata were proconvulsant. This prompted us to reevaluate the effects of intranigral muscimol in the kindling model with particular emphasis on the anterior substantia nigra pars reticulata. In amygdala kindled rats, muscimol was bilaterally infused into the anterior pars reticulata at doses of either 60 or 120 ng. Thirty minutes later, the threshold for induction of afterdischarges in the amygdala and the threshold for generalized seizures were determined in each rat. Furthermore, severity and duration of seizures at threshold currents were recorded. Unexpectedly, muscimol failed to increase seizure thresholds or to significantly reduce seizure severity or duration of motor seizures, although there was a moderate reduction in motor seizure duration in several rats. The data indicate that, in contrast to flurothyl seizures, in kindled rats the anterior pars reticulata of the substantia nigra is not a site at which muscimol causes robust anticonvulsant effects.