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d-Fenfluramine and d-norfenfluramine hypophagias do not require increased hypothalamic 5-hydroxytryptamine release
A O Oluyomi1, E L Gibson, A M Barnfield
1Department of Neurochemistry, Institute of Neurology, London, UK.
European Journal of Pharmacology
|October 13, 1994
Summary
d-Fenfluramine and its metabolite d-norfenfluramine reduce appetite in rats. However, their effects on feeding are not mediated by increased serotonin (5-HT) availability in the brain.
Area of Science:
- Neuroscience
- Pharmacology
- Physiology
Background:
- Serotonin (5-HT) is implicated in appetite regulation.
- Fenfluramine derivatives are known to affect feeding behavior.
Purpose of the Study:
- To investigate the role of 5-HT in the hypophagic effects of d-fenfluramine and its metabolite d-norfenfluramine.
- To determine if increased extracellular 5-HT mediates appetite suppression.
Main Methods:
- In vivo microdialysis in food-deprived rats.
- Administration of d-fenfluramine and d-norfenfluramine.
- Inhibition of 5-HT synthesis using p-chlorophenylalanine.
Main Results:
- d-Fenfluramine induced hypophagia and increased medial hypothalamic 5-HT.
- Pretreatment with a 5-HT synthesis inhibitor blocked the 5-HT increase but not the hypophagia.
- d-Norfenfluramine also caused hypophagia without increasing dialysate 5-HT.
Conclusions:
- The hypophagic effects of d-fenfluramine and d-norfenfluramine are not mediated by increased extracellular 5-HT availability.
- These findings challenge the direct role of enhanced serotonergic neurotransmission in the appetite-suppressing actions of these drugs.