Ghrelin-deficient mice have fewer orexin cells and reduced cFOS expression in the mesolimbic dopamine pathway under a...

Ghrelin is an orexigenic stomach peptide previously found to be important for the full display of anticipatory locomotor activity and hypothalamic neuronal activation that precedes a daily scheduled meal in mice. Ghrelin is also important for food-related motivation and seems to have direct effects in the mesocorticolimbic dopamine reward system. Here we hypothesized that neuronal activation in reward-related areas in anticipation of a scheduled meal could be mediated by elevated ghrelin induced by scheduled feeding, and therefore this would be attenuated in ghrelin receptor knock-out (GHSR KO) animals. We found that this was indeed the case for the ventral tegmental area and the shell, but not the core, of the nucleus accumbens. In addition, our results show a reduction in the proportion of activated orexin-immunoreactive (IR) neurons in GHSR KO animals in anticipation of the scheduled meal in comparison to the proportion of activated orexin neurons in wild type (WT) mice. Interestingly we observed that both GHSR and ghrelin KO mice had fewer orexin-IR cells than their WT littermates suggesting that lack of ghrelin or sensitivity to ghrelin may play a role in the development of the orexin system. Our data also suggest that ghrelin may mediate food anticipation, in part, by stimulating both the orexin system and the mesolimbic reward system.