The role of the central ghrelin system in reward (#61)
Ghrelin’s physiological role appears to extend beyond appetite and energy balance control to include reward-seeking behaviour. Given that ghrelin increases accumbal dopamine release, the midbrain dopamine pathways involved in incentive motivation (i.e. a projection from the ventral segmental area (VTA) to the nucleus accumbens (NAc)) is strongly implicated. Previously we showed that central ghrelin signaling is important for animals to receive reward from addictive drugs (including alcohol and cocaine) and also from palatable food. Central ghrelin signalling appears to be important for food preference, food anticipation, food reward and food motivation. More recently, we showed that ghrelin increases motivated behavior (lever pressing for a sucrose reward) in an operant conditioning paradigm when injected peripherally, icv or intra-VTA (but not intra-NAcc). By contrast, ghrelin administration to both the VTA and NAc increased the free feeding of chow1 . Ghrelin’s effects on food intake and food reward behaviour exerted at the levels of the VTA involve divergent pathways that can be teased apart using selective opioid, NPY 1R2 and dopamine D1/D2 receptor antagonists3 . We conclude that the emerging role for the central ghrelin system appears to include the enhancement of reward from both natural (e.g. food) and artificial reinforcers. The VTA but not the NAcc appears to be a direct target site for ghrelin’s effects on food motivation, and activation of the mesoaccumbal dopamine projection appears essential for ghrelin's effects on food motivated behaviour.
Research supported by EC Projects (FP7-KBBE-2009-3-245009, FP7-KBBE-2010-4-266408).
- Skibicka KP, Hansson C, Alvarez-Crespo M, Friberg PA, Dickso, SL. 2011. Ghrelin directly targets the ventral tegmental area to increase food motivation. Neuroscience 180, 129-137.
- Skibicka KP, Shirazi RH, Hansson C, Dickson SL, 2012 Ghrelin interacts with neuropeptide Y Y1 and opioid receptors to increase food reward. Endocrinology 153, 1194-1205.
- Skibicka KP, Shirazi RH, Rabasa-Papio C, Alvarez-Crespo M, Neuber C, Vogel H, Dickson SL. 2013 Divergent circuitry underlying food reward and intake effects of ghrelin: dopaminergic VTA-accumbens projection mediates ghrelin's effect on food reward but not food intake. Neuropharmacology 73, 274-283.