Role of serotonin and catecholamines in brain in the feeding suppressant effect of fluoxetine.

The hypophagic effect of fluoxetine was studied in rats, injected intracerebroventricularly with 150 micrograms/20 microliters 5,7-dihydroxytryptamine, to destroy serotonin-containing neurones or 250 micrograms/20 microliters 6-hydroxydopamine, to destroy catecholamine-containing neurones. The effect of various serotonin receptor antagonists was assessed as well. Neither neurotoxin significantly modified the effect of 20 mg/kg (i.p.) fluoxetine on food intake. Metergoline (1-5 mg/kg), (-)-propranolol (16 mg/kg) and ICS 205-930 (0.1 and 1 mg/kg) did not modify the hypophagic effect of fluoxetine, while mianserin (1 and 5 mg/kg), ritanserin (0.5 and 1 mg/kg) and xylamidine (3 mg/kg) slightly but significantly reduced it. While the mechanism by which some 5-HT receptor antagonists modify the effect of fluoxetine remains to be elucidated, it seems clear that 5-HT receptors hardly have any significant role in the ability of the drug to suppress food intake.