Springer Nature [academic journals on nature.com], Neuropsychopharmacology, 9(40), p. 2103-2112, 2015
DOI: 10.1038/npp.2015.67
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Studies implicate opioid transmission in hedonic and metabolic control of feeding, though roles for specific endogenous opioid peptides have barely been addressed. Here, we studied palatable liquid consumption in pro-enkephalin knockout (PENK KO) and β-endorphin-deficient (BEND KO) mice, and how the body weight of these mice changed during consumption of an energy-dense highly palatable "cafeteria diet". When given access to sucrose solution, PENK KOs exhibited fewer bouts of licking than wildtypes, even though the length of bouts was similar to that of wildtypes, a pattern that suggests diminished food motivation. Conversely, BEND KOs did not differ from wildtypes in the number of licking bouts, even though these bouts were shorter in length, suggesting that they experienced the sucrose as being less palatable. Additionally, licking responses in BEND, but not PENK, KO mice were insensitive to shifts in sucrose concentration or hunger. PENK, but not BEND, KOs exhibited lower baseline body weights compared to wildtypes on chow diet and attenuated weight gain when fed cafeteria diet. Based on this and related findings, we suggest endogenous enkephalins primarily set a background motivational tone regulating feeding behavior, whereas β-endorphin underlies orosensory reward in high need states or when the stimulus is especially valuable. Overall, these studies emphasize complex interplays between endogenous opioid peptides targeting mu receptors, such as enkephalins and endorphins, underlying the regulation of feeding and body weight, which might explain the poor efficacy of drugs that generally target mu opioid receptors in the long term control of appetite and body weight.Neuropsychopharmacology accepted article preview online, 10 March 2015. doi:10.1038/npp.2015.67.