Brain Serotonin, Carbohydrate-Craving, Obesity and Depression
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.
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