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      Temporal Changes in Prolactin and Corticosterone Response during Chronic Treatment with d-Fenfluramine

      ,

      Hormone Research in Paediatrics

      S. Karger AG

      <italic>d</italic>-Fenfluramine, Prolactin, Corticosterone, Serotonin, Anorexia

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          Abstract

          In order to elucidate the mechanism of development of tolerance to the anorectic effect during chronic treatment with d-fenfluramine (d-F ), we examined the temporal changes induced by d-Fin food intake and prolactin (PRL) and corticosterone secretion. Male Sprague-Dawley rats were treated for 14 days with d-F(2.5 mg/kg i.p.) or saline twice daily and were given free access to food and water. Groups of 8 rats were sacrificed 30 min after d-For saline injection at days 1, 4 and 14 for measurements of serum PRL and corticosterone. Food intake and weight gain were reduced significantly by d-Fduring the first 2–3 days of treatment but not thereafter. Compared with saline, d-Finitially increased PRL (57 ± 9 vs. 7 ± 0.7 ng/ml) and corticosterone (42 ± 2 vs. 14 ± 3 µg/dl) serum concentrations. At 4 days, PRL was still significantly increased (43 ± 5 vs. 10 ± 4 ng/ml) but corticosterone returned to basal levels. At 14 days, PRL and corticosterone concentrations in the d-Fgroup were not different from corresponding values in the saline group. To verify whether the loss of corticosterone and PRL responses to d-Fwas not due to a depletion of hormone stores, direct stimulation of corticosterone with corticotrophin and of PRL with metoclopramide were made at days 4 and 14, respectively. Corticotrophin (0.25 mg/kg i.p.) increased corticosterone concentrations similarly in d-F-treated (45 ± 8 µg/dl) and in saline-treated rats (51 ± 7 µg/dl). Metoclopramide (10 mg/kg s.c.) increased PRL concentrations to comparable levels in d-F - (38 ± 7 ng/ml) and in saline-treated rats (42 ± 7 ng/ml). These data indicate that chronic treatment with d-Fin the rat induces tolerance to the anorectic effect and the loss of the corticosterone-stimulating effect between days 1 and 4, whereas PRL response to d-Fis abolished later between days 4 and 14.

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          Author and article information

          Journal
          HRE
          10.1159/issn.0018-5051
          Hormone Research in Paediatrics
          S. Karger AG
          0018-5051
          2571-6603
          1989
          1989
          02 December 2008
          : 31
          : 4
          : 180-183
          Affiliations
          Metabolic Unit, Hôpital Notre-Dame, Centre de Recherche, Department of Nutrition, Université de Montréal, Québec, Canada
          Article
          181112 Horm Res 1989;31:180–183
          10.1159/000181112
          © 1989 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.

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