Allopregnanolone-induced modification of presynaptic basal and K+-induced [3H]-norepinephrine efflux from rat cortical slices during the estrous cycle

• Published in: Neuroendocrinology Vol. 68; no. 4; p. 264
• Main Authors: Belmar, J, Cuellar, C, Llona, I, Arancibia, S, Kusch, C, Tapia-Arancibia, L, Pinter, A, Pérez, H
• Format: Journal Article
• Language: English
• Published: Switzerland 01-10-1998
• Subjects: Adrenergic alpha-2 Receptor Antagonists; Animals; Cerebral Cortex - chemistry; Cerebral Cortex - metabolism; Drug Interactions; Estrus - drug effects; Female; Frontal Lobe - chemistry; Frontal Lobe - metabolism; Isomerism; Norepinephrine - analysis; Norepinephrine - secretion; Potassium - pharmacology; Pregnanolone - pharmacology; Pregnenolone - pharmacology; Presynaptic Terminals - drug effects; Rats; Rats, Sprague-Dawley; Tritium; Yohimbine - pharmacology
• ISSN: 0028-3835
• DOI: 10.1159/000054374

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(-9) M), 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.