Mediation of fluoxetine-induced hypophagia by feeding status, dopaminergic agonism, and malaise

The present studies examined the effects of the serotonin reuptake inhibitor fluoxetine (FLX) on sucrose solution consumption in free-fed and food-deprived rats. Further, these studies examined the degree to which the induction of malaise and the possible attenuation of dopamine (DA) may be associated with FLX-induced hypophagia. In Experiment 1, FLX, administered 30 min prior to testing, suppressed consumption in free-fed and food-deprived rats in a dose-dependent manner. When administered 4 h prior to testing, FLX similarly suppressed consumption in free-fed rats. However, food-deprived rats were significantly more resistant to the hypophagic effect of FLX, as compared to when it was administered 30 min prior to testing. This suggests that the effects of FLX on feeding may be qualitatively distinct when administered 30 min and 4 h prior to testing. In Experiment 2, FLX induced a conditioned taste aversion to a novel sucrose solution in a dose-dependent manner. These data indicate that FLX-induced hypophagia may be associated, to some extent, with the induction of malaise or an otherwise aversive state. In Experiment 3, the DA agonist amantadine suppressed hypophagia induced by FLX administered 4 h prior to testing, but did not affect hypophagia induced by FLX administered 30 min prior to testing. These data suggest that hypophagia induced by non-acute administration of FLX may be associated with the attenuation of DA activity. In summary, the experiments provided evidence for consideration of the treatment-test interval when evaluating the effects of FLX on feeding. In addition, these studies provide evidence that modulation of feeding by FLX is associated with at least two distinct mechanisms of action, the induction of malaise or alterations in DA activity. These data have significant implications for understanding the behavioral pharmacology of FLX and may suggest a pharmacologic means of attenuating the loss of appetite which is commonly observed in the clinical use of FLX