Reduction of feeding behavior by the serotonin uptake inhibitor sertraline.
Administration of the selective serotonin (5-HT) uptake inhibitor sertraline produced a dose-dependent reduction of food intake in rats. Doses of sertraline of 10 mg/kg or greater reduced the intake of solid pellets significantly (P less than 0.01) during the 1st hour of a 4-h feeding test in rats deprived of food and water for 24 h. Food intake during the remaining 3 h and water intake during the feeding test was unaffected by sertraline. Sertraline (2-18 mg/kg IP) also reduced milk consumption in food-deprived rats. Pretreatment with the nonselective 5-HT antagonists metergoline (2 mg/kg IP) or methysergide (3.3 mg/kg IP) blocked sertraline's inhibition of dry food intake, whereas pretreatment with the selective 5-HT2 receptor antagonist ketanserin (3.3 mg/kg IP) or the peripheral 5-HT2 antagonist xylamidine (2.5 mg/kg IP) failed to block sertraline's anorexic effect. The feeding-suppressant effect of 10 mg/kg sertraline was prevented following the destruction of central 5-HT neurons by the 5-HT neurotoxic agent, 5,7-dihydroxytryptamine (200 micrograms ICV). This result is consistent with sertraline's anorexic effect depending on intact 5-HT neurotransmission. Therefore, sertraline appears to reduce feeding by enhancing the action of endogenous serotonin at central synapses mediated by 5-HT1 rather than 5-HT2 receptors.
Lucki
I
I
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104-4283.
Kreider
M S
MS
Simansky
K J
KJ
D015057:1-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D004032:Diet; D004298:Dopamine / Q000378:metabolism; D004326:Drinking / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*; D020280:Sertraline; D013687:Telencephalon / Q000378:metabolism
D001679:Biogenic Amines; D009281:Naphthalenes; D012702:Serotonin Antagonists; D015116:5,7-Dihydroxytryptamine; D015057:1-Naphthylamine; D020280:Sertraline; D004298:Dopamine; D009638:Norepinephrine