Serotonergic control of the organization of feeding and satiety.
Studies in which serotonergic drugs were administered either systemically or directly into central sites have implicated 5-HT in the inhibitory control of feeding in mammals. In animal models and in humans, 5-HT agonists such as fenfluramine, fluoxetine and sertraline reduced the rate of eating and the size of meals in a manner suggesting that increasing serotonergic neurotransmission specifically enhanced satiation. In rodents, directly acting agonists at 5-HT1B, 5-HT2C or 5-HT2A receptors decreased food intake but by different behavioral mechanisms. Stimulation of the 1B and 2C subtypes may probe physiological roles in feeding and satiety. The former receptors may be involved primarily in regulating meal size and the latter more in controlling eating rate. Activation of both may be required for complete expression of behavioral satiety. By contrast, stimulating 2A sites may simply disrupt the continuity of feeding. Drugs that stimulate 5-HT1A autoreceptors increase food intake, presumably by acutely reducing the firing of serotonergic neurons in the brain. The hypothalamic paraventricular nucleus (PVN) has been proposed as an important terminal field in the forebrain that is involved in 5-HT's satiety role although recent studies implicate extra-PVN regions in this function. Peripherally administered 5-HT also decreases food intake in rats in a behaviorally specific manner. Studies with antagonists and with structural analogs of 5-HT revealed that 5-HT's peripheral satiety action involves 5-HT1-like and 5-HT2-like mechanisms. Thus, within and outside the brain, multiple pharmacological and behavioral mechanisms contribute to serotonergic functions in ingestion. The rich body of data from preclinical investigation in animals provides the foundation for therapeutic development in humans.
Simansky
K J
KJ
Department of Pharmacology, Medical College of Pennsylvania and Hahnemann University, Philadelphia 19129, USA.
D000818:Animals; D002490:Central Nervous System / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology*; D006801:Humans; D012528:Satiety Response / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*
D012701:Serotonin