The role of substantia nigra pars reticulata in modulating clonic seizures is determined by testosterone levels during the immediate postnatal period.

Neurobiol Dis

The Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Bronx, NY 10461, USA.

Published: January 2007

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GABAergic activation of substantia nigra pars reticulata (SNR) at postnatal day (PN) 15 has sex-specific features on seizure control in vivo and electrophysiological responses in vitro. In males, the GABA(A)-receptor agonist muscimol has proconvulsant effects and induces depolarizing responses. In females, muscimol has no effect on seizures and evokes hyperpolarizing responses. We determined the time period during which sex hormones must be present to produce the sex-specific muscimol effects on seizures and their influence on SNR GABA(A) receptor-mediated postsynaptic currents. Exposure to testosterone or its metabolites (estrogen or dihydrotestosterone) during PN0-2 in females or males castrated at PN0 was sufficient to produce proconvulsant muscimol effects but did not affect the in vitro GABA responses, which remained hyperpolarizing. The data suggest that the PN0-2 period is critical for the development of the seizure-controlling SNR system; the hormonal effect on seizure control is independent from their effect on GABA conductance.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1661598PMC
http://dx.doi.org/10.1016/j.nbd.2006.08.009DOI Listing

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