How does the brain know when carbohydrates have been or should be consumed? The answer to this question is not known, but one element in the explanation seems to be the neurotransmitter serotonin, one of a class of chemical mediators that may be released from a presynaptic neuron and that cause the transmission of a nerve impulse across a synapse to an adjacent postsynaptic neuron. In general, it has been found that drugs that selectively facilitate serotonin-mediated neurotransmission tend to cause weight loss, whereas drugs that block serotonin-mediated transmission often have the opposite effect: they often induce carbohydrate craving and consequent weight gain. Serotonin is a derivative of tryptophan, an amino acid that is normally present at low levels in the bloodstream. The rate of conversion is affected by the proportion of carbohydrates in an individual's diet: carbohydrates stimulate the secretion of insulin, which facilitates the uptake of most amino acids into peripheral tissues, such as muscles. Blood tryptophan levels, however, are unaffected by insulin, so the proportion of tryptophan in the blood relative to the other amino acids increases when carbohydrates are consumed. Since tryptophan competes with other amino acids for transport across the blood-brain barrier into the brain, insulin secretion indirectly speeds tryptophan's entry into the central nervous system where, in a special cluster of neurons, it is converted into serotonin. The level of serotonin in the brain in turn affects the amount of carbohydrate an individual chooses to eat. Rats that are allowed to choose among synthetic foods containing different proportions of carbohydrate and protein will normally alternate between foods containing mostly protein and those containing mostly carbohydrate. However, if rats are given drugs that enhance the effect of serotonin, the rats' carbohydrate intake is reduced. On the other hand, when rats are given drugs that interrupt serotonin-mediated neurotransmission, their brains fail to respond when carbohydrates are eaten, so the desire for them persists. In human beings a serotoninlike drug, d-fenfluramine, selectively suppresses carbohydrate snacking in people who crave carbohydrates. In contrast, drugs that block serotonin-mediated transmission or that interact with neurotransmitters other than serotonin have the opposite effect: they often induce carbohydrate craving and subsequent weight gain. People who crave carbohydrates report feeling refreshed and invigorated after eating a carbohydrate-rich meal, in contrast, those who do not crave carbohydrates become sleepy following a high-carbohydrate meal. These findings suggest that serotonin has other effects that may be useful indicators of serotonin levels in human beings.