Allopregnanolone-Induced Modification of Presynaptic Basal and K+-Induced [3H]-Norepinephrine Efflux from Rat Cortical Slices during the Estrous Cycle

Abstract

Superfused frontal slices of cerebral cortex were preloaded with [³H]-norepinephrine ([³H]NE). Basal [³H]NE efflux and K⁺-induced [³H]NE release were studied during the estrous cycle and in the presence of neurosteroids. Basal [³H]NE efflux showed estrous cycle-related variations, with lowest values found during estrus and diestrus II. Allopregnanolone (10^–9 M) potentiated basal [³H]NE efflux from the 1st minute of its application; the effect of the steroid was still present after 20 min. This effect was also dependent upon the estrous cycle, since basal [³H]NE efflux was mainly increased during estrus diestrus I, and to a lesser degree only during proestrus. During diestrus II and after ovariectomy, basal [³H]NE efflux was no longer affected by the neurosteroid. In the presence of yohimbine (10^–6 M), the effect of allopregnanolone on basal efflux was potentiated only during the first 3 min but vanished thereafter. Allopregnanolone (10^–9 M) potentiated the K⁺-induced [³H]NE release during estrus, but pregnenolone (10^–9 M) was ineffective, suggesting specificity of the neurosteroid. Yohimbine (10^–6 M) also potentiated K⁺-induced [³H]NE release. When applied simultaneously with allopregnanolone (10^–9M), a potentiating effect on [³H]NE release was observed. The present results suggest that allopregnanolone is a neurosteroid able to modulate norepinephrine release in the cerebral cortex in an estrous cycle-dependent manner, and that the effect could involve noradrenergic alpha-2 receptors.