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.


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.


CONCLUSIONS
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.
Prendergast
Mark A
MA
Department of Psychology, University of Nebraska at Omaha, NE 68182, USA.
Yells
David P
DP
Balogh
Scott E
SE
Paige
Stephen R
SR
Hendricks
Shelton E
SE
D000547:Amantadine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D015259:Dopamine Agents / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects*; D005473:Fluoxetine / Q000378:metabolism / Q000494:pharmacology*; D005508:Food Deprivation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D013395:Sucrose / Q000008:administration & dosage*
D000547:Amantadine; D015259:Dopamine Agents; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; D013395:Sucrose