Temporal changes in prolactin and corticosterone response during chronic treatment with d-fenfluramine.
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-F in 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-F or 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-F during the first 2-3 days of treatment but not thereafter. Compared with saline, d-F initially increased PRL (57 +/- 9 vs. 7 +/- 0.7 ng/ml) and corticosterone (42 +/- 2 vs. 14 +/- 3 micrograms/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-F group were not different from corresponding values in the saline group. To verify whether the loss of corticosterone and PRL responses to d-F was 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 micrograms/dl) and in saline-treated rats (51 +/- 7 micrograms/dl).(ABSTRACT TRUNCATED AT 250 WORDS)
Serri
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Metabolic Unit, Hôpital Notre-Dame, Québec, Canada.
Rasio
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D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism*; D004361:Drug Tolerance; D004435:Eating / Q000187:drug effects; D005277:Fenfluramine / Q000494:pharmacology*; D008297:Male; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology
D005277:Fenfluramine; D012701:Serotonin; D011388:Prolactin; D003345:Corticosterone