Developmental regulation of regional functionality of substantia nigra GABA(A) receptors involved in seizures

GABAergic (γ-aminobutyric acid) transmission in the substantia nigra pars reticulata is critical for seizure control. We tested the hypothesis that there is a differential regional distribution and functionality of nigral GABA(A) receptor sites that is developmentally regulated. In adult rats, we determined the effects on flurothyl seizures of (Z)-3-[(aminoiminomethyl)thio]prop-2-enoic acid (ZAPA, a presumed agonist of the low-affinity GABA(A) receptor site), bicuculline (an antagonist of the low-affinity GABA(A) receptor site) and γ-vinyl-GABA (a GABA-transaminase inhibitor), infused bilaterally in anterior or posterior substantia nigra pars reticulata. ZAPA infusions (8 μg) were anticonvulsant in anterior substantia nigra but proconvulsant in posterior substantia nigra. Bicuculline infusions (100 ng) were proconvulsant in anterior substantia nigra but ineffective in posterior substantia nigra. An anticonvulsant dose of γ-vinyI-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 biphasic: 2 μg was anticonvulsant while 8 μg was proconvulsant. There was no regional specificity. The data suggest that with maturation there is functional regional segregation of specific GABA(A) receptor subtypes involved in substantia nigra-mediated seizure control.