REGIONAL AND AGE-SPECIFIC EFFECTS OF ZOLPIDEM MICROINFUSIONS IN THE SUBSTANTIA-NIGRA ON SEIZURES

GABAergic (gamma-aminobutyric acid) transmission in the substantia nig ra pars reticulata (SNR) is critical for seizure control. Tn; SNR effe cts on seizures are site-specific within fh: SNR and developmentally r egulated. These ap-and site-specific effects may be due to differentia l regional distribution and functionality of SNR GABA(A) receptor site s. 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 B ZD(1) receptor site) microinfusions in the anterior or in the posterio r SNR (SNRanterior or SNRposterior, respectively) on flurothyl-induced clonic and tonic-clonic seizures. In SNRanterior, zolpidem microinfus ions were anticonvulsant but ineffective in SNRposterior against cloni c seizures. Microinfusions of zolpidem in SNRposterior or above SNR, d id not alter the threshold to clonic seizures. SNR microinfusions of z olpidem did not alter the threshold to tonic-clonic flurothyl-induced seizures. In 15 day old (PN 15) rats, the SNR microinfusions of zolpid em had anticonvulsant effects on clonic and tonic-clonic seizures. The re was no regional specificity. Microinfusions of zolpidem above the S NR, did not alter the threshold to clonic or tonic-clonic seizures. Ou r data demonstrate that the BZD(1) binding sites are involved in the S NR control of flurothyl seizures in adult and PN 15 male rats. (C) 199 8 Elsevier Science B.V. All rights reserved.