Objectives: 

The opioid system is well recognized as an important regulator of appetite and energy balance. Most studies have linked this system to feeding control through reward pathways, leaving its hypothalamic actions relatively unexplored. Moreover,it is unknown whether the opioid system is involved in ghrelin´s effects to regulate food intake. Therefore, in the present study, we aimed to determine: 1) if the opioid system modulates the orexigenic effect of ghrelin, and 2) potential neuronal and molecular mechanisms involved in the interaction between the opioid and ghrelin systems.

Materials: 

To accomplish this aim, we used male rats to inhibit KOR by pharmacological and genetic approaches, and studied the central ghrelin-induced effects on food intake and food reward.

Results: 

We demonstrate that ghrelin utilizes a hypothalamic KOR pathway to increase food intake. Pharmacological blockade of KOR attenuates the ghrelin-induced increase in food reward behavior and acute orexigenic effect of ghrelin. Inhibition of KOR expression in the hypothalamic arcuate nucleus is sufficient to blunt ghrelin-induced food intake. This new pathway is independent of ghrelin-induced AMPK activation, but modulates the levels of the transcription factors and orexigenic neuropeptides triggered by ghrelin to finally stimulate feeding.

Conclusions: 

Overall, our findings indicate that modulation of hypothalamic KOR is a new pathway for the orexigenic action of ghrelin.