Psychopharmacology

, Volume 96, Issue 3, pp 289–295

Reduction of feeding behavior by the serotonin uptake inhibitor sertraline

  • Irwin Lucki
  • Margaret S. Kreider
  • Kenny J. Simansky
Original Investigations

Abstract

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<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 μg 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.

Key words

Serotonin 5-HT1 receptor Feeding behavior Sertraline Antidepressant drugs Rats 

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References

  1. Anton AH, Sayre DF (1962) A study of the factors affecting the aluminum oxide trihydroxyindole procedure for the analysis of catecholamines. J Pharmacol Exp Ther 138:360–365Google Scholar
  2. Bendotti C, Samanin R (1987) The role of putative 5-HT1A and 5-HT1B receptors in the control of feeding in rats. Life Sci 41:635–642Google Scholar
  3. Blundell JE (1984) Serotonin and appetite. Neuropharmacology 23:1537–1551Google Scholar
  4. Blundell JE, Latham CJ (1978) Pharmacological manipulation of feeding behavior: possible influences of serotonin and dopamine on food intake. In: Garattini S, Samanin R (eds) Central mechanism of anorectic drugs. Raven Press, New York, pp 83–109Google Scholar
  5. Bray GA, York DA (1972) Studies on food intake in genetically obese rats. Am J Physiol 223:176–179Google Scholar
  6. Clineschmidt BV, McGuffin JC, Pflueger AB, Totaro JA (1978) A 5-hydroxytryptamine-like mode of anorectic action for 6-chloro-2-{1-piperazinyl}-pyrazine (MK-212). Br J Pharmacol 62:579–589Google Scholar
  7. Copp FC, Green AF, Hodson HF, Randall AW, Sim MF (1967) New peripheral antagonists of 5-hydroxytryptamine. Nature 214:200–201Google Scholar
  8. Fletcher PJ, Burton MJ (1986) Dissociation of the anorectic actions of 5-HTP and fenfluramine. Psychopharmacology 89:216–220Google Scholar
  9. Fuller RW, Owen JE (1981) Suppression of milk by the combination of fluoxetine and l-5-hydroxytyptophan in rats. Res Commun Chem Pathol Pharmacol 34:137–140Google Scholar
  10. Fuller RW, Snoddy HD, Mason NR, Hemricke-Luecke SK, Clemens JA (1981a) Substituted piperazines as central serotonin agonists: comparative specificity of the postsynaptic actions of quipazine and m-trifluoromethylphenylpiperazine. J Pharmacol Exp Ther 218:636–641Google Scholar
  11. Fuller RW, Snoddy HD, Mason NR, Owen JE (1981b) Disposition and pharmacological effects of m-chlorophenylpiperazine in rats. Neuropharmacology 20:155–162Google Scholar
  12. Glennon RA, Lucki I (1988) Behavioral models of serotonin receptor activation. In: Sanders-Bush E (ed) The serotonin receptors. Humana, New York (in press)Google Scholar
  13. Goudie AJ, Thornton EW, Wheeler TJ (1976) Effects of Lilly 110140, a specific inhibitor of serotonin uptake, on food intake and on 5-hydroxytryptophan induced anorexia. Evidence for serotonergic inhibition of feeding. J Pharm Pharmacol 28:318–320Google Scholar
  14. Green AR, Heal DJ (1985) The effects of drugs on serotonin-mediated behavioural models. In: Green AR (ed) Neuropharmacology of serotonin. Oxford University Press, Oxford, pp 325–365Google Scholar
  15. Koe BK, Weissman A, Welch WM, Browne RG (1983) Sertraline, 1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine, a new uptake inhibitor with selectivity for serotonin. J Pharmacol Exp Ther 226:686–700Google Scholar
  16. Leibowitz SF, Shor-Posner G (1986) Brain serotonin and eating behavior. Appetite [Suppl] 7:1–14Google Scholar
  17. Leysen JE, Awouters F, Kennis L, Laduron PM, Vandenberk J, Janssen PAJ (1981) Receptor binding profile of R 41468, a novel antagonist of 5-HT2 receptors. Life Sci 28:1015–1022Google Scholar
  18. Leysen JE, Niemegeers CJE, Van Nueten JM, Laduron PM (1982) (3H)Ketanserin (R41 468), a selective 3H-ligand for serotonin2 receptor binding sites. Mol Pharmacol 21:301–314Google Scholar
  19. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  20. Lucki I, Nobler MS, Frazer A (1984) Differential actions of serotonin antagonists on two behavioral models of serotonin receptor activation in the rat. J Pharmacol Exp Ther 228:133–139Google Scholar
  21. Pazos A, Hoyer D, Palacios JM (1985) The binding of serotonergic ligands to the porcine choroid plexus: characterization of a new type of serotonin recognition site. Eur J Pharmacol 106:539–546Google Scholar
  22. Pedigo NW, Yamamura HI, Nelson DL (1981) Discrimination of multiple [3H-]-5-hydroxytryptamine binding sites by the neuroleptic spiperone in rat brain. J Neurochem 36:220–226Google Scholar
  23. Peroutka SJ, Snyder SH (1979) Multiple serotonin receptors: Differential binding of [3H]5-hydroxytryptamine, [3H]lysergic acid diethylamine and [3H]spiroperidol. Mol Pharmacol 16:687–699PubMedGoogle Scholar
  24. Pollock JD, Rowland N (1981) Peripherally administered serotonin decreases food intake in rats. Pharmacol Biochem Behav 15:179–183Google Scholar
  25. Samanin R (1983) Drugs affecting serotonin and feeding. In: Curtis-Prior PB (ed) Biochemical pharmacology of obesity. Elsevier, Lausanne, pp 339–356Google Scholar
  26. Samanin R, Ghezzi D, Valzelli L, Garattini S (1972) The effects of selective lesioning of brain serotonin or catecholamine containing neurones on the anorectic activity of fenfluramine and amphetamine. Eur J Pharmacol 19:318–322Google Scholar
  27. Samanin R, Mennini T, Ferraris A, Bendotti C, Borsini F, Garattini S (1979) m-Chlorophenylpiperazine: a central serotonin agonist causing powerful anorexia in rats. Naunyn-Schmiedeberg's Arch Pharmacol 308:159–163Google Scholar
  28. Samanin R, Cacia S, Bendotti C, Borsini F, Borroni E, Invernizzi R, Pataccini R, Mennini T (1980) Further studies on the mechanism of serotonin-dependent anorexia in rats. Psychopharmacology 68:99–104Google Scholar
  29. Schechter LE, Simansky KJ (1988) 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI) exerts an anorexic action that is blocked by 5-HT2 antagonists in rats. Psychopharmacology 94:342–346Google Scholar
  30. Simansky KJ, Cohen BI, Eberle K (1987) Inhibition by 5-HT-2 antagonists of the anorexic actions of peripherally administered 5-hydroxytryptamine (5-HT) and 4-HT in rats. Soc Neurosci Abstr 13:15Google Scholar
  31. Weiss GF, Papadakos P, Knudson K, Leibowitz SF (1986) Medial hypothalamic serotonin: effects on deprivation and norepinephrine-induced eating. Pharmacol Biochem Behav 25:1223–1230Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • Irwin Lucki
    • 1
  • Margaret S. Kreider
    • 1
  • Kenny J. Simansky
    • 2
  1. 1.Behavioral Psychopharmacology Laboratory, Department of PsychiatryUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of PharmacologyMedical College of Pennsylvania at Eastern Pennsylvania Psychiatric InstitutePhiladelphiaUSA

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