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

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          Abstract

          Superfused frontal slices of cerebral cortex were preloaded with [<sup>3</sup>H]-norepinephrine ([<sup>3</sup>H]NE). Basal [<sup>3</sup>H]NE efflux and K<sup>+</sup>-induced [<sup>3</sup>H]NE release were studied during the estrous cycle and in the presence of neurosteroids. Basal [<sup>3</sup>H]NE efflux showed estrous cycle-related variations, with lowest values found during estrus and diestrus II. Allopregnanolone (10<sup>–9</sup>  M) potentiated basal [<sup>3</sup>H]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 [<sup>3</sup>H]NE efflux was mainly increased during estrus diestrus I, and to a lesser degree only during proestrus. During diestrus II and after ovariectomy, basal [<sup>3</sup>H]NE efflux was no longer affected by the neurosteroid. In the presence of yohimbine (10<sup>–6</sup>  M), the effect of allopregnanolone on basal efflux was potentiated only during the first 3 min but vanished thereafter. Allopregnanolone (10<sup>–9</sup>  M) potentiated the K<sup>+</sup>-induced [<sup>3</sup>H]NE release during estrus, but pregnenolone (10<sup>–9</sup>  M) was ineffective, suggesting specificity of the neurosteroid. Yohimbine (10<sup>–6</sup>  M) also potentiated K<sup>+</sup>-induced [<sup>3</sup>H]NE release. When applied simultaneously with allopregnanolone (10<sup>–9</sup> M), a potentiating effect on [<sup>3</sup>H]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.

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          Most cited references 7

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          Non-genomic and genomic effects of steroids on neural activity.

           Bruce McEwen (1991)
          Steroid hormones are recognized as producing their major long-term effects on cell structure and function via intracellular receptors acting on the expression of genes. There is now increasing evidence that steroids also affect the surface of cells and alter ion permeability, as well as release of neurohormones and neurotransmitters. Progesterone appears to be one of the most active of the steroids, and its naturally produced metabolites and some synthetic analogs show activities that are different from the parent steroid. Other steroids, such as estrogens and adrenal steroids and their naturally produced and synthetic analogs, also show membrane effects. Bruce McEwen reviews evidence that synergistic interactions occur between non-genomic and genomic actions of steroids.
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            Neurosteroids

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              In vitro progesterone effects on 3H-dopamine release from rat corpus striatum slices obtained under different endocrine conditions

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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                1998
                October 1998
                14 October 1998
                : 68
                : 4
                : 264-271
                Affiliations
                a Laboratory of Biochemical Pharmacology, P. Catholic University of Chile and b Laboratory of Neural Systems, University of Santiago, Chile; c Laboratory of Brain Plasticity EP 628, CRNS, University of Montpellier II, France
                Article
                54374 Neuroendocrinology 1998;68:264–271
                10.1159/000054374
                9772341
                © 1998 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 4, Tables: 1, References: 28, Pages: 8
                Categories
                Reproductive Neuroendocrinology

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