Effects of substantia nigra γ-vinyl-GABA infusions on flurothyl seizures in adult rats

There is evidence implicating the nigral γ-aminobutyric acid (GABA) system in the control seizures. Our previous studies have demonstrated that, in rat pups, intranigrally infused γ-vinyl-GABA (GVG, 5-20 μg) strongly suppresses flurothyl-induced tonic but not clonic seizures. Furthermore, nigral infusions of bicuculline or muscimol abolish the anticonvulsant effect of GVG. In this study, we report that in adult rats bilateral infusions of GVG (20 μg) into the substantia nigra pars reticulata (SNR) significantly elevated the thresholds for both clonic and tonic seizures induced by flurothyl. Lower doses (5 and 10 μg) did not significantly protect adult rats against seizures, but there was a significant effect of GVG dose. Unilateral infusion of GVG (20 μg) in the SNR did not alter the thresholds for flurothyl-induced seizures. Intranigral infusions of bicuculline following pretreatment with GVG abolished the protective effect of GVG on flurothyl-induced seizures, indicating that the anticonvulsant effect of GVG is most likely mediated by the nigral GABA_A receptor. Intranigral administration of muscimol after GVG pretreatment significantly suppressed flurothyl-induced seizures, but the combined effect of the two drugs was not as strong as that of GVG alone. The data suggest that GVG protects adult rats against flurothyl-induced seizures. In adults, however, the dose of GVG required to protect against both clonic and tonic seizures is higher than that needed in rat pup SNR.