Studies on the role of 5-HT receptors in satiation and the effect of d-fenfluramine in the runway test.
d-Fenfluranine has previously been shown to reduce food-rewarded runway behaviour in the rat, an effect thought to be mediated through activation of central 5-HT pathways. We now examined in more detail the mechanism by which d-fenfluramine reduces runway performance and food intake in the 15-trial runway test. The non-selective 5-HT receptor antagonist, metergoline (1.0 mg/kg), significantly antagonised the effect of d-fenfluramine (2.5 mg/kg) in the runway test. In contrast, neither ritanserin, the potent 5-HT2 and 5-HT1C receptor antagonist (0.5 mg/kg), nor the peripheral 5-HT receptor antagonist, xylamidine (3.0 mg/kg), attenuated the effect of d-fenfluramine in this test situation. Metergoline, but not ritanserin or xylamidine significantly increased runway performance when administered alone. These data indicate that d-fenfluramine reduces runway performance and food intake through activation of 5-HT1 receptors. In addition, blockade of 5-HT1 receptors can attenuate the development of satiation normally observed under control conditions in the runway test.
Neill
J C
JC
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Bendotti
C
C
Samanin
R
R
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D005247:Feeding Behavior / Q000187:drug effects*; D005277:Fenfluramine / Q000494:pharmacology*; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D016713:Ritanserin; D012527:Satiation / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D000578:Amidines; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D016713:Ritanserin; D008711:Metergoline; D005277:Fenfluramine; C005894:xylamidine