ReviewThe role of the central ghrelin system in reward from food and chemical drugs
Section snippets
The central ghrelin signalling system
The “central ghrelin signalling system” is recognised as an important CNS target for the control of food intake (Wren et al., 2000) and energy balance (Lall et al., 2001, Tschöp et al., 2000). Here we review the emerging concept that this system operates at the interface between neurobiological circuits involved in appetite and reward, increasing the incentive motivational value of both natural rewards (such as food) and artificial rewards (such as drugs of abuse).
We have coined the term
The physiological role of ghrelin: from hunger to reward-seeking
Soon after the discovery of ghrelin, the first endogenous ligand for GHS-R1A (Kojima et al., 1999), it became clear that this receptor is also a potentially interesting target for controlling food intake and obesity. In rodents, acute injection of ghrelin, peripherally or centrally, induces a rapid orexigenic response (Asakawa et al., 2001, Wren et al., 2000). It was also found that chronic stimulation of this receptor by ghrelin (Tschöp et al., 2000) or by synthetic growth hormone
The central ghrelin signalling system integrates with a key reward pathway
The mesolimbic dopamine pathway (Fig. 1) from the VTA to the N.Acc, that has a rather well-established role in incentive motivation (i.e. wanting) (Berridge and Robinson, 2003), is clearly an important component of the central ghrelin-responsive network. Ghrelin receptors are present in the VTA (Guan et al., 1997, Zigman et al., 2006), including a sub-population of dopamine cells in this region (Abizaid et al., 2006). Both central and intra-VTA administration of ghrelin induces an increase in
The central ghrelin signalling system is required for reward from drugs of abuse, including alcohol
Alcohol dependence, one of the major causes of death, is a chronic relapsing disease and is also a major cost for the society. Available treatments include medical, psychosocial as well as social interventions, which may help to increase time to relapse and to reduce the intake of alcohol. Alcohol dependence is a heterogeneous disorder where several signalling systems play important roles. By understanding the complex mechanisms underlying this disease new treatment strategies may be developed.
The central ghrelin signalling system is required for reward from food
In normal physiology, it seems likely that ghrelin does indeed operate as a circulating hunger hormone, conferring information to the brain about energy deficit and then interacting with key brain circuits to manifest a coordinated feeding response. This is achieved, in part, through activation of the aforementioned hypothalamic and brainstem circuits involved in energy homeostasis. Specifically, it has been shown that ghrelin increases food intake via activation of homeostatic feeding circuits
Conclusions
The exact circuitry and mechanisms through which ghrelin modulates the intake and seeking of rewards remains to be further elucidated, but likely involves actions at the level of the cholinergic–dopaminergic reward system. GHS-R1A is expressed pre- and post-synaptically in the VTA (Abizaid et al., 2006) as well as on cholinergic neurons in the LDTg (Dickson et al., 2010). Ghrelin injection into these discrete brain regions increases accumbal dopamine (Jerlhag et al., 2007) increases alcohol
Acknowledgments
Supported by the EU (FP7-HEALTH-2009-241592, FP7-KBBE-2009-3-245009; FP7-KBBE-2010-266408), Swedish Medical Research Council (K2007-54X-20328–013, K2006-21X-04247-33-3, 2009-S266, and 2009-2782), ALF/LUA grants from the Sahlgrenska Hospital Göteborg (SU7601, 7136, 7341, ALFGBG-138741, -148251), the Alcohol Research Council of the Swedish Alcohol Retailing Monopoly, The Swedish brain foundation, the foundations of Wilhelm and Martina Lundgren, Knut and Alice Wallenberg, The Adlerbert Research,
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