Brain Serotonin, Carbohydrate-Craving, Obesity and Depression

  • Richard J. Wurtman
  • J. J. Wurtman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 398)


Serotonin in the brain, and perhaps elsewhere, is involved in mechanisms that affect macronutrient selection, generate feelings of satiety, and, if malfunctioning, predispose to obesity. Drugs which increase the quantities of serotonin present within synapses can cause weight reduction. Such drugs presently include those that release the neurotransmitter by a direct action on nerve terminals (e.g., dexfenfluramine’s metabolite dexnorfenfluramine) or by activating serotoninergic neurons (e.g., nicotine); by activating post-synaptic serotonin receptors (e.g., dexnorfenfluramine); or by prolonging serotonin’s existence within synapses by blocking its reuptake (e.g., dexfenfluramine; fluoxetine, sertraline; paroxetine). Additional ways are known by which intrasynaptic serotonin levels can be augmented (e.g. increasing its synthesis with tryptophan; inhibiting its destruction by monoamine oxidase), and it can be anticipated that drugs acting at these loci will also become candidates for treating obesity.

Serotoninergic drugs act in at least three ways to facilitate weight loss: They accelerate the onset of satiety (Blundell, 1986), and enhance basal metabolic rate by about 100 calories per day (Fernstrom, 1989). They also inhibit the “carbohydrate craving” manifested by many people who are overweight or are becoming so (c.f., Wurtman and Wurtman, 1989). There is reason to believe that this inappropriate eating behavior actually constitutes a “serotonin hunger” by the brain, perhaps related to the number or activity of raphe neurons, in which case giving the serotoninergic drug might constitute a specific therapy for the etiologic process causing the obesity.


Brain Serotonin Serotonin Release Serotonin Synthesis Tryptophan Level Seasonal Affective Disorder 
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  1. Benwell M.E., Balfour D.J. and Anderson J.M., 1988, Evidence that tobacco smoking increases the density of (-)-[3H] nicotine binding sites in human brain, J. Neurochem.50: 1243.CrossRefGoogle Scholar
  2. Blundell J.E., 1986, Serotonin manipulations and the structure of feeding behavior, Appetite. (suppl): 39–56.Google Scholar
  3. Brzezinski A. A, Wurtman J.J., Wurtman R.J., Gleason R., Nader T., and Laferrere B., 1990, d-Fenfluramine suppresses the increased calorie and carbohydrate intakes and improves the mood of women with premenstrual syndrome, Obstet. Gynecol. 76:296.Google Scholar
  4. Fernstrom J.D. and Wurtman R.J.,. 1971 a, Brain serotonin content: Physiological dependence on plasma tryptophan levels, Science 173:149.Google Scholar
  5. Fernstrom J.D. and Wurtman R.J., 1971 b, Brain serotonin content: Increase following ingestion of carbohydrate diet, Science174: 1023.Google Scholar
  6. Fernstrom J.D., Wurtman R.J., Hammarstrom-Wiklund B., Rand W.M., Munro H.N. and Davidson C.S., 1979, Diurnal variations in plasma concentrations of tryptophan, tyrosine, and other neutral amino acids: Effect of dietary protein intake, Am. J. Clin. Nutr.32: 1912.Google Scholar
  7. Fernstrom M.H., 1989, Depression, antidepressants, and body weight, Ann. N. Y. Acad. Sci.575: 31.CrossRefGoogle Scholar
  8. Fuller R.W., Snoddy H.D. and Robertson D.W., 1988, Mechanisms of effects of d-fenfluramine on brain serotonin metabolism in rats: Uptake inhibition versus release, Pharmacol. Biochem. Behav.30: 715.CrossRefGoogle Scholar
  9. Gardier A. and Wurtman R.J., 1991, Persistent blockade of potassium-evoked serotonin release from rat frontocortical terminals after fluoxetine administration, Brain Res. 540: 325.CrossRefGoogle Scholar
  10. Gardier A., Kaakkola S., Erfurth A. and Wurtman R.J., 1992, Effects of methiothepin on changes in brain serotonin release induced by repeated administration of high doses of anorectic drugs, Brain Jtes. 588 (1): 67.CrossRefGoogle Scholar
  11. Guy-Grand G., Apfelbaum M., Crepaldi G., leFebvre P., Greis A. and Turner P., 1989, International trial of long-term dexfenfluramine in obesity. Lancet2: 1142.CrossRefGoogle Scholar
  12. Kalia M., 1991, Reversible, short-lasting, and dose-dependent effect of (+)-fenfluramine on neocortical serotonergic axons, Brain Res. 548: 111.CrossRefGoogle Scholar
  13. Kalucy R.J., 1980, Drug-induced weight gain, Drugs19: 268.CrossRefGoogle Scholar
  14. Kim W., Kelay J.,Judd J., Marshall M.W., Metz W. and Prather E.S., 1987, Evaluation of long-term dietary intakes of adults consuming self-selected diets, Am. J. Clin. Nutr.40: 1327.Google Scholar
  15. Laferrere B. and Wurtman R.J., 1989, Effect of d-fenfluramine on serotonin release in brains of anesthetized rats, Brain Res. 504: 258.CrossRefGoogle Scholar
  16. Leibowitz S.F., Weiss G.F. and Shor-Posner G., 1988, Hypothalamic serotonin: Pharmacological, biochemical and behavioral analyses of its feeding-suppressive action, Clin. Neuropharmacol.11. S51.Google Scholar
  17. Lieberman H.R., Caballero B. and Finer N., 1986, The composition of lunch determines afternoon plasma tryptophan ratios in humans, J. Neural Transm.65: 211.CrossRefGoogle Scholar
  18. Moses P.L. and Wurtman R.J., 1984, The ability of certain anorexic drugs to suppress food consumption depends on the nutrient composition of the test diet, Life Sci. 35: 1297.CrossRefGoogle Scholar
  19. McCue H., Jr., 1981, The 1979 build and blood pressure study, in: “Medical Aspects of Mortality Statistics”, H. Bostrom, N. Ljungstedt, eds., Almquist and Wiksell International, Stockholm.Google Scholar
  20. Molliver D.C. and Molliver M.E., 1990, Anatomic evidence for a neurotoxic effect of (+)- fenfluramine upon serotoninergic projections in the rat, Brain Res. 551: 165.CrossRefGoogle Scholar
  21. Pardridge W. and Flere G., 1990, Transport of tryptophan into brain from the circulating, albumin-bound pool in rats and in rabbits, J. Neurochem.54: 971.CrossRefGoogle Scholar
  22. Pi-Sunyer F., 1991, Health implications of obesity, Am. J. Clin. Nutr. 53: 1595S.Google Scholar
  23. Ribeiro E., Bettiker R., Bogdanov M. and Wurtman R.J., 1993, Effects of systemic nicotine on serotonin release in rat brain, Brain Res. 621: 311.CrossRefGoogle Scholar
  24. Rosenthal N.E., Sack D.A.,Gillin J.C, Lewey A.J., Goodwin F.K., Davenport Y., Mueller P.S., Newsome D.A., and Wehr T.A., 1984, Seasonal Affective Disorder: A description of the syndrome and preliminary findings with light therapy, Arch. Gen. Psychiatry41. 72.Google Scholar
  25. Rosenthal N., Genhart M., Caballero B., Jacobsen F.M., Skwerer R.G., Coursey R.D., Rogers S., and Spring B.J., 1989, Psychobiological effects of carbohydrate- and protein-rich meals in patients with Seasonal Affective Disorder and normal controls, Biol. Psychiatry.25: 1029.CrossRefGoogle Scholar
  26. Schaechter J.D. and Wurtman R.J., 1990, Serotonin release varies with brain tryptophan levels, Brain Res. 532: 203.CrossRefGoogle Scholar
  27. Schuster C.R., Lewis M. and Seiden L.S., 1986, Fenfluramine neurotoxicity, Psychopharmacol. Bull.22: 148.Google Scholar
  28. Spring B., Wurtman J., Gleason R. and Kessler K., 1991, Weight gain and withdrawal symptoms after smoking cessation: A preventive intervention using d-fenfluramine, Health Psychol. 10: 216.CrossRefGoogle Scholar
  29. Toornvliet A.C., Pijl H., Hopman E., Pietero M. and Meinders A.E., 1994, The identification of obese patients sensitive to a serotoninergic drug, Abstract Presented at the 7th International Congress on Obesity, Toronto, Canada, August 20 - 25.Google Scholar
  30. Trouvin J.H,. Gardier A.M, Chanut E., Pages N. and Jacquot C., 1993, Time course of brain serotonin metabolism after cessation of long-term fluoxetine treatment in the rat, Life Sci. 52: 187.Google Scholar
  31. Wack J. and Rodin J., 1982, Smoking and its effect on body weight and the systems of caloric regulation, Am. J. Clin. Nutr.35: 366.Google Scholar
  32. Wurtman J. J., Wurtman R.J., Reynolds S., Tsay R., and Chew B., 1987, d-Fenfluramine suppresses snack intake among carbohydrate cravers but not among non carbohydrate cravers, Int. J. of Eating Disord. 6:687.Google Scholar
  33. Wurtman R.J. and Wurtman J.J., 1989, Carbohydrates and depression, Sci. Am. January: 68–75.Google Scholar

Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • Richard J. Wurtman
    • 1
    • 2
  • J. J. Wurtman
    • 1
  1. 1.Department of Brain and Cognitive Sciences and Clinical Research CenterMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.M.I.T.CambridgeUSA

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