Sex and the substantia nigra: administration, teaching, patient care, and research

The immature brain is most susceptible to the development of seizures. The substantia nigra may play a crucial role in the control of seizures as a function of age. In the adult substantia nigra pars reticulata (SNR), there are two regions that mediate opposing effects on seizures after infusions of GABA(A) agents. One region is located in the anterior SNR, and localized muscimol infusions mediate anticonvulsant effects. These anticonvulsant effects use a circuitry that may involve the ventromedial thalamic nucleus, the deep layer of the superior colliculus, or both. The second region is in the posterior SNR, and muscimol infusions produce proconvulsant effects, perhaps mediated by the striatum, the globus pallidus, the deep layer of the superior colliculus, or all three. In developing male rats, only the proconvulsant region is present up to the age of 21 days. In ongoing studies, it has been shown that, in the male rat, the transition from the immature to mature SNR-mediated seizure control occurs between the ages of 25 and 30 days, just before adolescence. In male rats castrated on the day of birth, the ensuing depletion of testosterone accelerates the development of the anterior SNR with its anticonvulsant features. Castration does not alter the development of the proconvulsant region. In the developing female SNR, muscimol infusions produce only anticonvulsant effects. The data indicate that gonadal hormones may have an important role in the maturation of systems involved in the containment of seizures.