Dietary sugars and non-caloric sweeteners elicit different homeostatic and hedonic responses in the brain.

•Glucose elicits an immediate deactivation of the hypothalamus.•Sucrose and fructose elicit a delayed deactivation of the hypothalamus•The non-caloric sweetener sucralose elicits a transient hypothalamic response•In the ventral tegmental area, sucralose elicits a very similar activation to plain water ingestion•The natural sugars appeared to only elicit a transient, if any, increase in ventral tegmental area activity