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.