EFFECT OF DEXFENFLURAMINE ON SACCHARIN DRINKING - BEHAVIORAL AND PHARMACOLOGICAL STUDIES

We have previously reported that the 5-hydroxytryptamine (5-HT) releas er/reuptake blocker dexfenfluramine suppresses voluntary ethanol intak e. 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. Sa ccharin was made available for 2 h daily across a wide concentration r ange chosen to promote varying degrees of intake. Following stable lev els of intake, the behaviour of vehicle-pretreated rats was assessed i mmediately prior to (anticipatory/preparatory phase) and during (consu matory phase) saccharin access. These behaviours were compared and con trasted with those produced following dexfenfluramine pretreatment at the optimally preferred saccharin concentration (0.2%). In a prelimina ry study the effects of various 5-HT antagonists were also examined ag ainst the dexfenfluramine response. The present results suggest that d exfenfluramine 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 concen tration. Behavioural analysis indicated that the profile of the dexfen fluramine (0.5- and 1-mg/kg doses only) suppression of the 0.2% soluti on was similar to that observed in vehicle-pretreated rats presented w ith saccharin solutions of lesser palatability to this concentration. Pharmacological studies indicated a 5-HT1 (non-5-HT1c) receptor involv ement in the dexfenfluramine response. These studies imply that at cer tain doses dexfenfluramine may produce a subtle alteration in the moti vation to consume a preferred fluid.