Scope: A high-fat, but low-fiber, diet is associated with obesity and cognitive dysfunction, while dietary fiber supplementation can improve cognition. Methods and results: This study examines whether dietary fibers, galacto-oligosaccharides (GOS) and resistant starch (RS), could prevent high-fat (HF)-diet-induced alterations in neurotransmitter receptor densities in brain regions associated with cognition and appetite. Rats are fed a HF diet, HF diet with GOS, HF diet with RS, or a low-fat (LF, control) diet for 4 weeks. Cannabinoid CB1 (CB1R) and 5HT1A(5HT1AR) and 5-HT2A(5HT2AR) receptor binding densities are examined. In the hippocampus and hypothalamus, a HF diet significantly increases CB1R binding, while HF + GOS and HF + RS diets prevented this increase. HF diet also increases hippocampal and hypothalamic 5-HT1AR binding, while HF + GOS and HF + RS prevented the alterations. Increased 5-HT2Abinding is prevented by HF + GOS and HF + RS in the medial mammillary nucleus. Conclusions: These results demonstrate that increased CB1R, 5-HT1AR and 5-HT2AR induced by a HF diet can be prevented by GOS and RS supplementation in brain regions involved in cognition and appetite. Therefore, increased fiber intake may have beneficial effects on improving learning and memory, as well as reducing excessive appetite, during the chronic consumption of a HF (standard Western) diet.