Ghrelin directly targets the ventral tegmental area to increase food motivation

The role of the central ghrelin system in reward from food and chemical drugs

“…Consistent with this, we found that central intraventricular (Skibicka et al 2011a) or intra-VTA (Skibicka et al 2011b) injection of ghrelin to satiated rats increased motivation for a sucrose reward, assessed in an operant conditioning paradigm. In these studies animals show motivated behaviour by working increasingly hard (pressing a lever) to obtain a sweet treat.…”

“…In this powerful test of reward, the animals no longer show preference for the food (sweet treat)-paired environment, suggesting that the GHS-R1A antagonists suppress food reward. Moreover, we found that motivated behaviour for food reward can also be suppressed by intra-ventricular or intra-VTA administration of JMV2959 (Skibicka et al 2011a;Skibicka et al 2011b). Thus, as reviewed elsewhere (Egecioglu et al 2011;Skibicka and Dickson 2011), GHS-R1A provides a potential target for the treatment of problematic over-eating.…”

“…GHS-R1A is expressed pre-and post-synaptically in the VTA (Abizaid et al 2006) as well as on cholinergic neurons in the LDTg . Ghrelin injection into these discrete brain regions increases accumbal dopamine (Jerlhag et al 2007) increases alcohol intake and food intake as well as motivated behaviour for palatable foods Skibicka et al 2011b). Indeed, pharmacological manipulations within the VTA reduce reward induced by ghrelin, additive drugs as well as for palatable food Jerlhag et al 2009;Jerlhag et al 2010a;Skibicka et al 2011b).…”

“…Activation of hypothalamic and brainstem areas could be of importance for ghrelin's effects on homeostatic feeding that is driven by metabolic need. However, ghrelin may also enhance non-homeostatic feeding by interacting with key reward systems Perello et al 2010;Skibicka et al 2011a;Skibicka et al 2011b). The reward system, specifically the mesolimbic dopamine system, mediates a state of well-being of natural and chemical reinforcers; it enhances motivation behaviours such as food-seeking and is involved in the development of addiction to drugs of abuse (Engel et al 1988;Hansen et al 1991;Schultz et al 1997).…”

“…When consumed in excess and over time food can cause the same brain neuroadaptations as drug abuse (Grigson 2002). Indeed, human imaging studies show that there is an underlying disruption in the reward systems in the brain (Holden 2001;Potenza et al 2003;, as well as in brain regions important for inhibitory control The identification of the reward circuits as a key target for ghrelin has therefore led to the unexpected discovery that the central ghrelin signalling system is required for reward induced by addictive drugs aur and Ryabinin 2010;Tessari et al 2007;Wellman et al 2005) as well as palatable food Perello et al 2010;Skibicka et al 2011a;Skibicka et al 2011b). The ghrelin receptor, GHS-R1A, has emerged therefore as a relevant therapeutic target for addictive behaviours.…”