Behavioural evidence that d-fenfluramine-induced anorexia in the rat is not mediated by the 5-HT1A receptor subtype.
These studies investigated the involvement of the 5-HT1A receptor in mediating d-fenfluramine-induced anorexia in the rat. Non-deprived, d-fenfluramine-treated (3.0 mg/kg) rats consumed a reduced amount of a palatable wet mash and showed a temporal advance in the behavioural sequence consistent with satiety. Thus, rats treated with d-fenfluramine ceased feeding and began resting before corresponding controls. Pretreatment with the selective 5-HT1A receptor antagonist WAY-100,635 (1.0 mg/kg) had no effect on either the reduced mash consumption or behavioural satiety sequence of d-fenfluramine-treated animals at a dose which was found to attenuate the anorexia induced by the 5-HT1A receptor agonist 8-OH-DPAT (0.5 mg/kg). Pretreatment with the non-selective 5-HT antagonist metergoline (1.0 mg/kg) attenuated the d-fenfluramine-induced reduction of mash consumption and the advanced offset of feeding. Metergoline pretreatment had no effect on the advanced onset of resting observed in d-fenfluramine-treated animals. These data suggest that d-fenfluramine reduces food intake, perhaps by enhancing satiety, via a mechanism which does not involve the 5-HT1A receptor subtype. The implications of these results to the utility of the behavioural satiety sequence as a measure of postprandial satiety are discussed.
Vickers
S P
SP
Laboratory of Experimental Psychology, University of Sussex, Brighton, UK.
Clifton
P G
PG
Dourish
C T
CT
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000378:metabolism*; D001067:Appetite Depressants / Q000494:pharmacology*; D001070:Appetitive Behavior / Q000187:drug effects*; D004347:Drug Interactions; D005277:Fenfluramine; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology*
D001067:Appetite Depressants; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D008711:Metergoline; D005277:Fenfluramine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin