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      Effects of Prenatal Morphine and Adult Estrogen Administration on μ-Opioid Inhibition of Norepinephrine Release from Hypothalamic Slices

      a , a,b

      Neuroendocrinology

      S. Karger AG

      Opiates, Preoptic area, Catecholamines, Gonadal steroids

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          Abstract

          The present study tested the hypotheses that exposure to morphine in utero (10 mg/kg twice a day on gestation days 11–18) and acute estrogen treatment in adulthood alter µ-opioid regulation of hypothalamic norepinephrine (NE) release in sexually mature rats. Both basal and KCl-stimulated NE releases were measured in superfused hypothalamic and preoptic area (POA) slices preloaded with <sup>3</sup>H-NE. The µ-opioid receptor agonist D-Ala<sup>2</sup>, MePhe<sup>4</sup>-Gly-ol<sup>5</sup>-enkephalin (DAMGO; 10 or 100 n M) or the opioid antagonist naloxone (1 µ M) was applied to some slices 15 min prior to KC1 stimulation. Prenatal morphine had no effect on basal or KCl-stimulated release of preloaded <sup>3</sup>H-NE from hypothalamic and POA slices from adult male progeny. Neither the µ-opioid agonist DAMGO nor the nonspecific antagonist naloxone significantly affected KCl-evoked overflow of <sup>3</sup>H-NE in slices from either brain region of male rats. Adult female offspring were ovariectomized (OVX), and some were injected with a replacement dose of estrogen 48 h prior to sacrifice. Prenatal morphine had no effect on basal or KCl-stimulated release of <sup>3</sup>H-NE from hypothalamic or POA slices or on the response of slices to opioid drugs. Estrogen treatment modestly increased KCl-evoked release of <sup>3</sup>H-NE from POA slices from females. Moreover, there was a significant interaction between opioid drugs and estrogen treatment on KCl-evoked overflow of <sup>3</sup>H-NE. In hypothalamic and POA slices from OVX females, DAMGO reduced KCl-evoked efflux of <sup>3</sup>H-NE. This inhibitory effect of DAMGO was not apparent in slices from estrogen-treated females. In addition, naloxone increased KCl-stimulated NE release in slices from both hypothalamus and POA of estrogen-treated female rats but not control OVX females. Thus, prenatal exposure to morphine does not alter basal, KCl-evoked or µ-opioid modulation of NE efflux from hypothalamic or POA slices in adult progeny of either sex. However, treatment of adult, OVX females with estrogen attenuates µ-opioid inhibition and promotes the appearance of naloxone facilitation of KCl-evoked <sup>3</sup>H-NE release from hypothalamic and POA slices.

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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
          : 1
          : 61-68
          Affiliations
          Departments of aPsychiatry and bNeuroscience, Albert Einstein College of Medicine, Bronx, N.Y., USA
          Article
          126936 Neuroendocrinology 1996;63:61–68
          10.1159/000126936
          8839356
          © 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: 8
          Categories
          Regulation of Hypothalamic Neurons

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