Yang: The neurobiology of sugar cravings 105 tive appetite rating in normal weight adult Food reward consists of two branches: males [33]. Aspartame also increased subjec- sensory and postingestive [41]. In humans, tive hunger ratings compared to glucose or gustatory information perceived by taste re- water [34]. Glucose preload reduced the per- ceptors on the tongue ascends through the ceived pleasantness of sucrose, but aspartame thalamus and eventually terminates in the did not [34]. In another study, aspartame, ace- anterior insula/frontal operculum and the or- sulfame potassium, and saccharin were all as- bitofrontal cortex [43,44]. Amygdala makes sociated with heightened motivation to eat reciprocal connections along all levels of the and more items selected on a food preference gustatory pathway. Mesolimbic dopamine list [35]. Aspartame had the most pronounced system is also crucial for the hedonic recog- effect, possibly because it does not have a bit- nition of the stimulus and feeling of satisfac- ter aftertaste. Unlike glucose or sucrose, tion following ingesting food with pleasant which decreased the energy intake at the test tastes [41,45,46,47]. meal, artificial sweetener preloads either had The postingestive component depends no effect [33,35] or increased subsequent en- on metabolic products of the food [48]. ergy intake [36,37]. Those findings suggest When food deprived, rats preferred glucose that the calorie contained in natural sweeten- solution over saccharin solution, regardless ers may trigger a response to keep the overall of flavor that can be masked by adding qui- energy consumption constant. nine [49]. The postingestive effects con- Human research must rely on subjective tained both positive and negative neuronal ratings and voluntary dietary control. Rodent signals separate from mechanical satiety models helped elucidate how artificial sweet- [48]. For moderately concentrated nutrients, eners contribute to energy balance. Rats con- rats learned to prefer the food associated ditioned with saccharin supplement had with regular feeding than “sham feeding,” in significantly elevated total energy intake and which the ingested food flowed out of the gained more weight with increased body adi- body through a gastric fistula. However, rats posity compared to controls conditioned with did not show preference if highly concen- glucose [38]. Saccharin-conditioned rats also trated nutrients were used [48]. Hypothala- failed to curb their chow intake following a mus has been shown to mediate the sweet pre-meal. When a flavor was arbitrarily postingestive food reward [41,50]. Hypo- associated with high or low caloric content, thalamus secretes various neuropeptides to rats ate more chow following a pre-meal with regulate energy, osmotic balance, and feed- the flavor predictive of low caloric content ing behavior. [39]. These studies pose a hypothesis: Incon- The separation of brain areas in food re- sistent coupling between sweet taste and ward is not exclusive, as dopaminergic acti- caloric content can lead to compensatory vation was associated in sucrose preference overeating and positive energy balance. in mice lacking sweet taste perception [51]. Increasing evidence suggests that arti- ficial sweeteners do not activate the food re- NEURONAL RESPONSES TO ward pathways in the same fashion as ARTIFICIAL SWEETENERS natural sweeteners. Lack of caloric contri- What drives the desire to eat? Food re- bution generally eliminates the postingestive ward shares brain circuitry with other pleas- component. Functional magnetic imaging in urable activities such as sex and drug normal weight men showed that glucose in- administration [40,41]. It also shares the gestion resulted in a prolonged signal de- same behavioral paradigm with other forms pression in the hypothalamus. This response of addiction: binging, withdrawal, craving, was not observed with sucralose ingestion and cross-sensitization [41]. A period of ab- [50]. Natural and artificial sweeteners also stinence greatly increased sucrose self-ad- activate the gustatory branch differently. The ministration in rats, similar to binging sweet taste receptor, a heterodimer of two G behavior in humans [42]. protein coupled transmembrane receptors,