Abstracts

RATIONALE: The substantia nigra pars reticulata (SNR) plays a critical role in the control of seizures. The SNR effects on flurothyl seizures are sex- and age-specific. Pharmacological studies revealed that, in postnatal day-PN30 rats, there are two distinct GABAA-sensitive regions within the SNR: the anterior region (SNRanterior) and the posterior region (SNRposterior). In male rats, infusions of muscimol into these two regions have opposite effects on flurothyl seizures. In female rats, infusions of muscimol in the SNRanterior are anticonvulsant but infusions in the SNRposterior have no effect. There is only one functional region at PN15. Nigral infusions of muscimol at PN15 are proconvulsant in males but have no effect on seizures in females. The aim of this study was to determine whether there are sex- and age-specific differences in the distribution and expression of GABA in the SNR.
METHODS: Free floating sagittal sections of the SNR were processed for immunohistochemistry with GABA antibody in male and female rats at PN30 and PN15. Immunoreactive (ir) neurons were counted. We used optical density (OD) measurements to determine the level of immunoreactivity in the SNRanterior and SNRposterior.
RESULTS: In both age groups and sexes, there were fewer GABA-ir neurons in the SNRanterior compared to SNRposterior. In both sexes at PN30, neurons in the SNRanterior had higher ODs than neurons in the SNRposterior. At PN15, there were no regional differences in the ODs. However, in each age group, the female SNR had more GABA-ir cells, and higher ODs than the male SNR.
CONCLUSIONS: The data support the notion that the SNR is a sexually dimorphic structure. Sex- and age-related differences in the SNR in GABA immunoreactivity support the findings of sex- and age-specific effects of GABAergic drug infusions in the SNRanterior and the SNRposterior in the control of seizures.