The role of ghrelin in reward-based eating

Abstract

The peptide hormone ghrelin acts in the central nervous system as a potent orexigenic signal. Not only is ghrelin recognized as playing an important role in feeding circuits traditionally thought of as affecting body weight homeostasis, but also an accumulating number of scientific studies have identified ghrelin as being a key regulator of reward-based, hedonic eating behaviors. In the current article, we review ghrelin's orexigenic actions, the evidence linking ghrelin to food reward behavior, potential mechanisms by which ghrelin mediates reward-based eating behavior, and those studies suggesting an obligatory role for ghrelin in the changed eating behaviors induced by stress.

Figure 1. Model of ghrelin action on the mesolimbic reward circuitry in the rodent brain

Depicted is a sagittal view of the rodent brain in which regions implicated in ghrelin’s regulation of the rewarding value of food are highlighted. Signaling within dopaminegic neurons of the ventral tegmental area (VTA) mediate ghrelin’s actions on food reward. Ghrelin induces overflow of dopamine within the nucleus accumbens (NAc). VTA neurons also send projections to the lateral hypothalamic area (LHA), amygdala (Amyg), hippocampus (Hipp) and medial prefrontal cortex (mPFC), although engagement of these brain regions by ghrelin acting via the VTA is currently unclear. A role for cholinergic (ACh) neurons emanating from the laterodorsal tegmental area (LDTg) in the regulation of this circuitry has also been proposed. Other signals, such as NPY, orexins, glutamate and endocannabinoids, have been shown to modulate ghrelin’s action on food reward, although the anatomic locations of neurons producing these signals remain unclear. Solid lines and dotted lines represent established and hypothesized connections, respectively.