Clinical studies involving alcohol‐dependent subjects have shown a reversible increase in plasma levels of ghrelin during the initial phase of abstinence (Wurst et al. 2007), as well as correlations between elevated ghrelin levels and craving during alcohol withdrawal (Addolorato et al. 2006; Leggio et al. 2012). However, the circuitry and mechanism by which ghrelin modulates these cravings in humans remain to be elucidated. In light of published pre‐clinical results, a possible route could involve direct actions on the cholinergic‐dopaminergic reward link. Firstly, Ghsr are expressed in nodes of this link including the nucleus accumbens (NAc) (Landgren et al. 2011b), on dopaminergic neurons in the ventral tegmental area (VTA) (Abizaid et al. 2006) and on cholinergic neurons in the laterodorsal tegmental area (LDTg) (Dickson et al. 2010). Secondly, local administration of ghrelin into either the VTA or LDTg increases the locomotor activity, releases accumbal dopamine and increases alcohol consumption in mice (Jerlhag et al. 2007, 2009). Another possible route by which the ghrelin signaling system may alter the sensitivity of the mesolimbic dopamine system and the ability of addictive drugs to
