Brain opioid peptide systems are known to play an important role in motivation, emotion, attachment behaviour, the response to stress and pain, and the control of food intake. Opioid peptides within the ventral striatum are thought to play a key role in the latter function, regulating the affective response to highly palatable, energy-dense foods such as those containing fat and sugar. It has been shown previously that stimulation of mu opiate receptors within the ventral striatum increases intake of palatable food. In the present study, we examined enkephalin peptide gene expression within the striatum in rats that had been given restricted daily access to an energy-dense, palatable liquid food, chocolate Ensure®. Rats maintained on an ad libitum diet of rat chow and water were given 3-h access to Ensure® daily for two weeks. One day following the end of this period, preproenkephalin gene expression was measured with quantitative in situ hybridization. Compared with control animals, rats that had been exposed to Ensure® had significantly reduced enkephalin gene expression in several striatal regions including the ventral striatum (nucleus accumbens), a finding that was confirmed in a different group with Northern blot analysis. Rats fed this regimen of Ensure® did not differ in weight from controls. In contrast to chronic Ensure®, acute ingestion of Ensure® did not appear to affect enkephalin peptide gene expression. These results suggest that repeated consumption of a highly rewarding, energy-dense food induces neuroadaptations in cognitive-motivational circuits.