Central manipulation of dopamine receptors attenuates the orexigenic action of ghrelin

Abstract

Objective Recent evidence suggests that ghrelin, a peptidic hormone stimulating food intake, interacts with the dopamine signaling. This interaction has been demonstrated to modulate several effects of ghrelin, such as locomotor activity, memory, and food intake. Ghrelin increases dopamine levels in the shell of the nucleus accumbens stimulating food intake, while ablation of the ghrelin receptor attenuates the hypophagia caused by the activation of dopamine receptor 2. However, it is not known whether the orexigenic action of ghrelin is due to changes in central dopamine receptors.

Materials and methods We used Sprague–Dawley rats injected with different dopamine receptor agonists, antagonists, and ghrelin.

Results We demonstrate that the specific central blockade of dopamine receptor 1, 2, and 3 (D1, D2, and D3, respectively) reduces the orexigenic action of ghrelin. Similarly, specific central stimulation, either singly of dopamine receptor 1 or dopamine receptors 2 and 3 simultaneously, causes a significant decrease in ghrelin-induced food intake. Co-stimulation of all three receptors (D1, D2, and D3) also led to a marked attenuation in ghrelin-induced food intake. Importantly, the reduction in ghrelin-induced feeding was not caused by malaise or any type of behavioral alteration.

Conclusion Taken together, these data indicate that dopamine receptors play an important role in acute stimulation of feeding behavior induced by central injection of ghrelin.