ALLOPREGNANOLONE-INDUCED MODIFICATION OF PRESYNAPTIC BASAL AND K-INDUCED [H-3]-NOREPINEPHRINE EFFLUX FROM RAT CORTICAL SLICES DURING THE ESTROUS-CYCLE()

Superfused frontal slices of cerebral cortex were preloaded with [H-3] -norepinephrine ([H-3]NE). Basal [H-3]NE efflux and Kf-induced [H-3]NE release were studied during the estrous cycle and in the presence of neurosteroids. Basal [H-3]NE efflux showed estrous cycle-related varia tions, with lowest values found during estrus and diestrus II. Allopre gnanolone (10(-9) M) potentiated basal [H-3]NE efflux from the Ist min ute of its application; the effect of the steroid was still present af ter 20 min. This effect was also dependent upon the estrous cycle, sin ce basal [H-3]NE efflux was mainly increased during estrus diestrus I, and to a lesser degree only during proestrus. During diestrus II and after ovariectomy, basal [H-3]NE efflux was no longer affected by the neurosteroid. In the presence of yohimbine (10(-6) M), the effect of a llopregnanolone on basal efflux was potentiated only during the first 3 min but vanished thereafter. Allopregnanolone (10(-9) M) potentiated the K+-induced [H-3]NE release during estrus, but pregnenolone (10(-9 ) M) was ineffective, suggesting specificity of the neurosteroid. Yohi mbine (10(-6) M) also potentiated K+-induced [H-3]NE release. When app lied simultaneously with allopregnanolone (10(-9) M), a potentiating e ffect on [H-3]NE release was observed. The present results suggest tha t allopregnanolone is a neurosteroid able to modulate norepinephrine r elease in the cerebral cortex in an estrous cycle-dependent manner, an d that the effect could involve noradrenergic alpha-2 receptors.