Sweet taste pleasantness is modulated by morphine and naltrexone
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Rodent models highlight the key role of μ-opioid receptor (MOR) signaling in palatable food consumption. In humans, however, the effects of MOR stimulation on eating and food liking remain unclear.
Here, we tested sweet pleasantness experience in humans following MOR drug manipulations. We hypothesized that behaviors regulated by the endogenous MOR system would be enhanced by MOR agonism and decreased by antagonism. In line with rodent findings, we expected the strongest drug effects for the sweetest (high-calorie) sucrose stimuli. As very sweet stimuli are considered aversive by many people (called sweet dislikers), we also assessed whether MOR manipulations affect pleasantness ratings of sucrose-water stimuli differently depending on subjective and objective value.
In a bidirectional psychopharmacological cross-over study, 49 healthy men underwent a sweet taste paradigm following double-blind administration of the MOR agonist morphine, placebo, and the opioid antagonist naltrexone.
As hypothesized, MOR stimulation with morphine increased pleasantness of the sweetest of five sucrose solutions, without enhancing pleasantness of the lower-sucrose solutions. For opioid antagonism, an opposite pattern was observed for the sweetest drink only. The observed drug effects on pleasantness of the sweetest drink did not differ between sweet likers and dislikers.
The bidirectional effect of agonist and antagonist treatment aligns with rodent findings showing that MOR manipulations most strongly affect the highest-calorie foods. We speculate that the MOR system promotes survival in part by increasing concordance between the objective (caloric) and subjective (hedonic) value of food stimuli, so that feeding behavior becomes more focused on the richest food available.
KeywordsOpioid system Food Morphine Naltrexone Human
We are grateful to Øivind Skare for help with setting up the mixed effects analyses. We thank Jeppe Riegels, Ingunn Olsen, Olga Chelnokova, and Hedda Gjertsen for help with data collection. We thank Elisabeth Øiestad, Vigdis Vindenes, and Liliana Bach at the Norwegian Institute for Public Health for help with determining medication doses and analyses of biological data. The study is indirectly supported by Aleris Healthcare, Norway, financing the research position of Frode Willoch at the University of Oslo.
The study was supported by grants from the Norwegian Research Council (ES455867) and a Ph.D. grant from the South-Eastern Norway Regional Health Authority (2013053).
Conflict of interests
The authors declare no competing or conflicting financial interests.
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