Opioid antagonists block the positive hedonic response to food taste and are potent inhibitors of palatability-driven feeding. However, the specific brain regions within which opioid peptide secretion contributes to the maintenance of palatability-driven feeding have not been clearly established. In the present study, c-Fos immunohistochemistry was used to identify regions rostral to the hindbrain that display cellular activation in response to a palatable meal and the meal-paired environment. Further, it was determined whether any of the cellular responses could be prevented by pretreating animals with naltrexone. Twenty brain regions known to be involved in gustation, appetite and reward functions were examined. Ingestion of the palatable meal (3.0 g of 30% shortening, 20% sucrose and 50% powdered Purina rat chow) increased Fos-like immunoreactivity (FLI) in lateral hypothalamus (LH), ventral tegmentum (VTA) and medial preoptic area (MPOA), and decreased FLI in the habenula (Hab). The meal-paired environment increased FLI in the VTA and nucleus accumbens shell (NAC shell). Naltrexone (1.0 mg/kg, i.p.) did not block consumption of the small meal but did prevent all of the distinctive increases in FLI induced by the meal and meal-paired environment. Since naltrexone, alone, increased FLI in VTA, NAC shell, central amygdala (ceA) and laterodorsal bed nucleus of the stria terminalis (BSTLD), the blunting of ingestion reward by naltrexone may result from direct or transsynaptic activating effects on opponent neuronal activity within this highly interconnected set of structures that mediate and modulate reward.