Effect of dexfenfluramine on saccharin drinking: behavioural and pharmacological studies

We have previously reported that the 5-hydroxytryptamine (5-HT) releaser/reuptake blocker dexfenfluramine suppresses voluntary ethanol intake. To further analyse the generality of these findings, in the present study we examined the effect of equivalent doses of dexfenfluramine (0.5-2.5 mg/kg) on the intake of another preferred fluid, saccharin. Saccharin was made available for 2 h daily across a wide concentration range chosen to promote varying degrees of intake. Following stable levels of intake, the behaviour of vehicle-pretreated rats was assessed immediately prior to (anticipatory/preparatory phase) and during (consumatory phase) saccharin access. These behaviours were compared and contrasted with those produced following dexfenfluramine pretreatment at the optimally preferred saccharin concentration (0.2%). In a preliminary study the effects of various 5-HT antagonists were also examined against the dexfenfluramine response. The present results suggest that dexfenfluramine produced a dose-related suppression of saccharin intake at doses similar to those which reduced ethanol intake. However, the magnitude of this suppression was similar across each saccharin concentration. Behavioural analysis indicated that the profile of the dexfenfluramine (0.5- and 1-mg/kg doses only) suppression of the 0.2% solution was similar to that observed in vehicle-pretreated rats presented with saccharin solutions of lesser palatability to this concentration. Pharmacological studies indicated a 5-HT1 (non-5-HT1C) receptor involvement in the dexfenfluramine response. These studies imply that at certain doses dexfenfluramine may produce a subtle alteration in the motivation to consume a preferred fluid.