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Title: Interaction of the hypothalamic-pituitary-adrenal axis with the serotoninergic anorectic D-Fenfluramine
Author: Maclean, Ross John
ISNI:       0000 0001 3615 7315
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 1997
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Arase et al. (1989) demonstrated that, in Fenfluoramine-treated rats, adrenalectomy increased body weight loss and prevented the recovery of food intake that otherwise occurs 8-10 days after the beginning of drug treatment. Results presented in this thesis show that the effects of adrenalectomy on fenfluramine action were eventually reversed if the animals were studied for longer than the 8-10 day period undertaken in the above study. This thesis describes the results of a study designed to investigate the effects of adrenalectomy on D-Fenfluramine (D-Fen) in the regulation of food intake and energy balance. The aim was to establish possible loci and mechanism(s) for these effects and to evaluate the results in terms of possible value for clinical usage. The pharmacological and physiological systems associated with the modulation of D-Fen and adrenalectomy in the reduction of food intake and body weight were investigated. The results presented in this thesis support the hypothesis that there is a potentiation of D-Fen action in adrenalectomised rats. The increased half-lives of D-Fen and D-Nor-Fenfluramine (D-Nor0-Fen), following adrenalectomy, promotes increased body weight loss, a reduction in food intake, decreased efficiencies of food deposition, an increase in the activity of hypothalamic corticotrophin releasing factor and of both the hypothalamic and hippocampal serotinergic system. In conclusion, removal of corticosterone, by adrenalectomy, impairs the pathway for the metabolism and subsequent elimination of D-Fen and D-Nor-Fen. The pharmacological effect of D-Fen (and D-Nor-Fen) was enhanced, following adrenalectomy, since brain and serum levels of drug and metabolite remain elevated for a longer period. The reversibility of the anorectic effects of fenfluramine observed by Arase et al. (1989) in intact animals is therefore retained in the adrenalectomised animals, however due to the mechanism postulated above, the time required for this to occur is increased.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Metabolism; Weight loss; Adrenalectomy