DEVELOPMENTAL REGULATION OF REGIONAL FUNCTIONALITY OF SUBSTANTIA-NIGRA GABA(A) RECEPTORS INVOLVED IN SEIZURES

GABAergic (gamma-aminobutyric acid) transmission in the substantia ni, ora pars reticulata is critical for seizure control. We tested the hyp othesis that there is a differential regional distribution and functio nality of nigral GABA(A) receptor sites that is developmentally regula ted. In adult rats, we determined the effects on flurothyl seizures of (Z)-3-[(aminoiminomethyl)thio]prop-2-enoic acid (ZAPA, a presumed ago nist of the low-affinity GABA(A) receptor site), bicuculline (an antag onist of the low-affinity GABA(A) receptor site) and gamma-vinyl-GABA (a GABA-transaminase inhibitor), infused bilaterally in anterior or po sterior substantia nigra pars reticulata. ZAPA infusions (8 mu g) were anticonvulsant in anterior substantia nigra but proconvulsant in post erior substantia nigra. Bicuculline infusions (100 ng) were proconvuls ant in anterior substantia nigra but ineffective in posterior substant ia nigra. An anticonvulsant dose of gamma-vinyl-GABA, when infused in anterior substantia nigra, was proconvulsant when infused in posterior substantia nigra. In 15 day old rats, the effects of ZAPA were biphas ic: 2 mu g was anticonvulsant while 8 mu g was proconvulsant. There wa s no regional specificity. The data suggest that with maturation there is functional regional segregation of specific GABA(A) receptor subty pes involved in substantia nigra-mediated seizure control.