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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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          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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          Hormone Research in Paediatrics
          S. Karger AG
          02 December 2008
          : 31
          : 4
          : 180-183
          Metabolic Unit, Hôpital Notre-Dame, Centre de Recherche, Department of Nutrition, Université de Montréal, Québec, Canada
          181112 Horm Res 1989;31:180–183
          © 1989 S. Karger AG, Basel

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