Abstracts

Rationale: The substantia nigra pars reticulata (SNR) plays an important role in seizure control. We observed that the delta subunit protein expression decreases with age regardless of sex. The decrease of this subunit, crucial for generation of tonic conductance, is accompanied by reduction of tonic inhibition accordingly. We have also found that the alpha1 subunit mRNA expression in the SNR is higher in female rats and that it increases with age in both sexes. Therefore, we asked what are the effects of GABAA agonists THIP (4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol, Gaboxadol) and muscimol on tonic currents in GABAergic neurons in male and female rats in different ages. Methods: We studied three groups of Sprague-Dawley male and female rats at postnatal days (P) 5-9, 12-15 and 28-32. Whole-cell patch clamp recordings were made from electrophysiologically identified nigral GABAergic cells in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione and AP-5. THIP and muscimol were bath-applied and enhancement of tonic currents was measured as the change in baseline current before and after drugs took effect. Results: THIP response depends on age and sex, the maximal enhancement being in P5-9 and P12-15 males and minimal in P28-32 group in both sexes. On the other hand, muscimol induced changes in tonic current were greater in females than in males but we did not find age-related differences. Conclusions: The tonic GABA current present in GABAergic SNR neurons under natural conditions can be enhanced in an age and sex specific manner with different sensitivity to THIP and muscimol. The observed different responses to tested drugs suggest different GABAA receptors subunit composition. Given the importance of SNR GABAergic neurons in seizure control, these findings could facilitate treatment of epilepsy based on sex and maturational state of the brain. Supported by grants NS 20253, NS045243 from NINDS and an RSRF grant.