Progress in assessing the role of serotonin in the control of food intake

S. Garattini, A. Bizzi, S. Caccia, T. Mennini, R. Samanin

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There is evidence that serotonin inhibits food intake, particularly intake of carbohydrate and that induced by activation of catecholamine-containing neurons in different brain circuits. An agent that has contributed considerably to the hypothesis of a role of serotonin in feeding is fenfluramine, used as an anorexigenic drug in obese people. Experiments using synaptosomal preparations for studying monoamine uptake and release have shown that d-fenfluramine is more potent than l isomer in inhibiting serotonin uptake while d-norfenfluramine preferentially releases serotonin from a reserpine-insensitive compartment. Studies on brain monoamine release and metabolism in intact animals have shown that d and l isomers of fenfluramine at relatively low doses have a specific action on brain serotonin and catecholamines, respectively. Several findings suggest that d-fenfluramine and d-norfenfluramine cause anorexia by increasing the availability of serotonin at postsynaptic receptors. Evidence has recently been provided that d-fenfluramine uses preferentially serotonin1 sites, particularly of the serotonin(1B) type, in the rat brain to cause anorexia in this animal species. Activation of serotonin(1A) sites by agents such as 8-OH-DPAT and buspirone instead has been shown to cause overeating. It is suggested that serotonin(1B) sites in the hypothalamus and serotonin(1A) sites in the serotonin neurons of the midbrain raphe nuclei mediate these effects. Evidence is provided that [3H]d-fenfluramine binding to rat brain membranes is different from serotonin uptake sites ([3H]imipramine binding) and serotonin receptors. It is, however, displaced by some drugs using serotonin to cause anorexia, raising the possibility that it is somewhat related to serotonin mechanisms involved in feeding control. These studies provide evidence that the serotoninergic system in the brain is a likely target for drugs affecting food intake and suggest new ways to develop novel and potent strategies for the treatment of clinical hyperphagia and anorexia.

Original languageEnglish
JournalClinical Neuropharmacology
Issue numberSUPPL. 1
Publication statusPublished - 1988

ASJC Scopus subject areas

  • Clinical Neurology
  • Pharmacology (medical)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)


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