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      Time-Dependent Changes in Rat Brain Neuroactive Steroid Concentrations and GABA A Receptor Function after Acute Stress

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          Abstract

          The time courses of changes in rat brain neuroactive steroid concentrations and γ-aminobutyric acid type A (GABA<sub>A</sub>) receptor function elicited by acute stress were investigated in animals exposed to CO<sub>2</sub> for 1 min, a treatment known to induce stress in rats and panic attacks in humans. Inhalation of CO<sub>2</sub> induced increases in cerebral cortical steroid concentrations, the time dependence of which varied with the steroid examined. Thus, progesterone and deoxycorticosterone showed maximal increases (10- and 4-fold, respectively) 10 min after CO<sub>2</sub> inhalation and had returned to basal values by 30 and 60 min, respectively. In contrast, pregnenolone and 3<sub>α</sub>-hydroxy-5<sub>α</sub>-pregnan-20-one (allopregnanolone) concentrations showed maximal increases (+174 and +200%, respectively) at 30 min, were still higher than control at 60 min and returned to control values 120 min after stress. Inhalation of CO<sub>2</sub> also resulted in increases in plasma steroid concentrations, most of which peaked at 30 min and had returned to control values by 60 min. A parallel analysis of the stress-induced changes in GABA<sub>A</sub> receptor function, assessed either biochemically by t-[<sup>35</sup>S]butylbicyclophosphorothionate ([<sup>35</sup>S]TBPS) binding to cerebral cortical membranes or behaviorally by the punished responding score in Vogel’s test, showed that the effects of CO<sub>2</sub> inhalation on both parameters were maximal (+51 and –40%, respectively) after 10 min; the behavioral reaction returned to normal after 60 min, whereas [<sup>35</sup>S]TBPS binding had returned to control values 120 min after stress. The results show that: (a) the maximal increase in the brain concentrations of allopregnanolone, a potent and efficacious positive modulator of GABA<sub>A</sub> receptors, occurred at a time (30 min) when both conflict behavior and [<sup>35</sup>S]TBPS binding begun to decrease, and (b) both allopregnanolone concentrations and [<sup>35</sup>S]TBPS binding had returned to control values 120 min after CO<sub>2</sub> inhalation. The data are thus consistent with a physiological role of neuroactive steroids in restoring GABAergic tone after stress.

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          Author and article information

          Journal
          NEN
          Neuroendocrinology
          10.1159/issn.0028-3835
          Neuroendocrinology
          S. Karger AG
          0028-3835
          1423-0194
          1996
          1996
          09 April 2008
          : 63
          : 2
          : 166-172
          Affiliations
          aDepartment of Experimental Medicine, University of Rome ‘Tor Vergata’, Rome, Italy; bDepartment of Experimental Biology, Chair of Pharmacology, University of Cagliari, Italy; cDepartment of Psychiatry, University of California, San Diego, Calif., USA
          Article
          126953 Neuroendocrinology 1996;63:166–172
          10.1159/000126953
          9053781
          © 1996 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
          Pages: 7
          Categories
          Gonadotropin-Releasing Hormone and Gonadal Steroid Feedback

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