Serotonin plays an important role in the regulation of food and water intake, and drugs that inhibit the uptake of this neurotransmitter have been used as appetite suppressors. As the clinical usage of anorectics necessarily involves chronic drug administration, the effects of chronic treatment in animals are likely to be of greater clinical relevance than acute drug effects. Besides, little effort has been made to examine whether these effects interact with stressful situations, such as isolation. We have therefore examined the effects of fluoxetine, a selective 5-HT reuptake inhibitor, and gepirone, a 5-HT1A agonist, on body weight in isolated and in group-housed rats during 3 weeks of daily treatment. Gepirone caused an increase in body weight only in isolated rats. On the other hand, fluoxetine caused a significant reduction in body weight in both singly- and group-housed animals. The effects of these serotonergic agents were more prominent during the first week of treatment. From the data obtained in this study, it is suggested that increased 5-HT transmission produced by fluoxetine during chronic administration seems to be crucial for the appetite-regulating action of 5-HT, and this hypophagic effect does not seem to be dependent on the activation of 5-HT1A receptors since it was not shared by gepirone. Moreover, a concomitant stressful situation, such as isolation, interferes with the action of gepirone on feeding behavior. The hyperphagic effects of chronic regimen with gepirone in isolated animals are probably due to the concurrent reduction of the 5-HT transmission caused by this anxiogenic condition at the earlier stages of treatment. On the other hand, the anorectic effects of fluoxetine do not seem to interact with the stressful situations caused by isolation.
