Regional and age specific effects of zolpidem microinfusions in the substantia nigra on seizures

GABAergic (gamma-aminobutyric acid) transmission in the substantia nigra pars reticulata (SNR) is critical for seizure control. The SNR effects on seizures are site-specific within the SNR and developmentally regulated. These age- and site-specific effects may be due to differential regional distribution and functionality of SNR GABA(A) receptor sites. We investigated the role of GABA/benzodiazepine (BZD) receptors in the SNR in the control of seizures as a function of age. In adult rats, we determined the effects of bilateral zolpidem (an agonist of the BZD1 receptor site) microinfusions in the anterior or in the posterior SNR (SNRanterior or SNRposterior, respectively) on flurothyl-induced clonic and tonic-clonic seizures. In SNRanterior, zolpidem microinfusions were anticonvulsant but ineffective in SNRposterior against clonic seizures. Microinfusions of zolpidem in SNRposterior or above SNR, did not alter the threshold to clonic seizures. SNR microinfusions of zolpidem did not alter the threshold to tonic-clonic flurothyl-induced seizures. In 15 day old (PN 15) rats, the SNR microinfusions of zolpidem had anticonvulsant effects on clonic and tonic-clonic seizures. There was no regional specificity. Microinfusions of zolpidem above the SNR, did not alter the threshold to clonic or tonic-clonic seizures. Our data demonstrate that the BZD1 binding sites are involved in the SNR control of flurothyl seizures in adult and PN 15 male rats.