Fluoxetine differentially suppresses sucrose solution consumption in free-fed and food-deprived rats - Reversal by amantadine

Background: Clinical use of fluoxetine and similar medications is often associated with appetite suppression and weight loss that may warrant drug discontinuation. It is unclear, however, if fluoxetine-induced consummatory suppression may be influenced by factors such as dietary status and if appetite suppressant effects of fluoxetine may be pharmacologically attenuated. Material/Methods: Fluoxetine (0.5-10 mg/kg, i.p.) was administered to free-fed and 24 hr food-deprived adult male rats either 30 min or 4 hr prior to presentation of a sucrose solution (10% v/v). Further, amantadine (5-10 mg/kg, i.p.) and fluoxetine (5 mg/kg) were both administered either 30 min or 4 hr prior to sucrose solution presentation and intake of the solution was assessed after 2 hours of exposure. Results: Fluoxetine (2-10 mg/kg) administration significantly reduced sucrose solution intake in both free-fed and food-deprived rats. However, a brief treatment-test interval (30 min) resulted in a greater suppression of intake and food-deprived rats were more resistant to the suppressant effects of fluoxetine than were sated rats. Finally, the suppressant effect of fluoxetine were reversed by acute administration of amantadine (8 mg/kg) prior to sucrose solution presentation, a dose producing no inherent stimulation of consumption. Conclusion: Acute fluoxetine administration produces a reduction in palatable substance intake that is decreased in potency with a longer treatment-test interval, an effect likely not related to pharmacokinetic considerations. Further, fluoxetine-induced consummatory suppression is reduced by prior food-deprivation. Evidence that the dopamine agonist amantadine reversed fluoxetine-induced consummatory suppression suggests a role for dopaminergic antagonism in the appetite suppressant effects of fluoxetine.