The Ghrelin Signalling System Is Involved in the Consumption of Sweets

Department of Pharmacology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
PLoS ONE (Impact Factor: 3.23). 03/2011; 6(3):e18170. DOI: 10.1371/journal.pone.0018170
Source: PubMed


The gastric-derived orexigenic peptide ghrelin affects brain circuits involved in energy balance as well as in reward. Indeed, ghrelin activates an important reward circuit involved in natural- as well as drug-induced reward, the cholinergic-dopaminergic reward link. It has been hypothesized that there is a common reward mechanism for alcohol and sweet substances in both animals and humans. Alcohol dependent individuals have higher craving for sweets than do healthy controls and the hedonic response to sweet taste may, at least in part, depend on genetic factors. Rat selectively bred for high sucrose intake have higher alcohol consumption than non-sucrose preferring rats and vice versa. In the present study a group of alcohol-consuming individuals selected from a population cohort was investigated for genetic variants of the ghrelin signalling system in relation to both their alcohol and sucrose consumption. Moreover, the effects of GHS-R1A antagonism on voluntary sucrose-intake and operant self-administration, as well as saccharin intake were investigated in preclinical studies using rodents. The effects of peripheral grelin administration on sucrose intake were also examined. Here we found associations with the ghrelin gene haplotypes and increased sucrose consumption, and a trend for the same association was seen in the high alcohol consumers. The preclinical data show that a GHS-R1A antagonist reduces the intake and self-administration of sucrose in rats as well as saccharin intake in mice. Further, ghrelin increases the intake of sucrose in rats. Collectively, our data provide a clear indication that the GHS-R1A antagonists reduces and ghrelin increases the intake of rewarding substances and hence, the central ghrelin signalling system provides a novel target for the development of drug strategies to treat addictive behaviours.

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Available from: Dag S Thelle
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    • "There is a possibility that the orexigenic peptide reduces alcohol intake due to alcohol’s caloric rather than rewarding properties. This appears less likely since the GHS-R1A antagonist JMV2959 reduces the intake of saccharine, another reward without calories [68], suppresses parameters strictly reflecting reward namely locomotor stimulation and conditioned place preference [55] as well as attenuates reward induced by other addictive dugs without caloric content (see Sect. 2.4). "
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    ABSTRACT: Food intake and appetite are regulated by various circulating hormones including ghrelin and glucagon-like-peptide 1 (GLP-1). Ghrelin, mainly released from the stomach, increases food intake, induces appetite, enhances adiposity as well as releases growth hormone. Hypothalamic "ghrelin receptors" (GHS-R1A) have a critical role in food intake regulation, but GHS-R1A are also expressed in reward related areas. GLP-1 is produced in the intestinal mucosa as well as in the hindbrain in response to nutrient ingestion. This gut-brain hormone reduces food intake as well as regulates glucose homeostasis, foremost via GLP-1 receptors in hypothalamus and brain stem. However, GLP-1 receptors are expressed in areas intimately associated with reward regulation. Given that regulation of food and drug intake share common neurobiological substrates, the possibility that ghrelin and GLP-1 play an important role in reward regulation should be considered. Indeed, this leading article describes that the orexigenic peptide ghrelin activates the cholinergic-dopaminergic reward link, an important part of the reward systems in the brain associated with reinforcement and thereby increases the incentive salience for motivated behaviors via this system. We also review the role of ghrelin signaling for reward induced by alcohol and addictive drugs from a preclinical, clinical and human genetic perspective. In addition, the recent findings showing that GLP-1 controls reward induced by alcohol, amphetamine, cocaine and nicotine in rodents are overviewed herein. Finally, the role of several other appetite regulatory hormones for reward and addiction is briefly discussed. Collectively, these data suggest that ghrelin and GLP-1 receptors may be novel targets for development of pharmacological treatments of alcohol and drug dependence.
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    • "Ghrelin is a stomach-derived orexigenic hormone that modulates food intake and energy balance via homeostatic brain circuits that reside in the hypothalamic area (Briggs and Andrews, 2011; Diéguez et al., 2010). Recent evidence suggests a role of ghrelin and its receptor, growth hormone secretagogue receptor (GHSR), in food reward behavior that is tightly associated with the mesolimbic dopamine system (Skibicka and Dickson, 2011; Landgren et al., 2011). Besides the nutritional state, ghrelin has an impact on the neuronal circuit that signals the reward value of food ingested to dopamine neurons in the ventral tegmental area (VTA) (Abizaid, 2009; Skibicka and Dickson, 2011). "

    Full-text · Dataset · Oct 2013
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    • "Numerous studies have shown that ghrelin increases operant lever pressing for various food rewards including HFD, sucrose, peanut butter, and chocolate pellets in both mice and rats (Perello et al., 2010; Skibicka et al., 2011). In terms of the functional outcomes in response to decreased ghrelin activity , ghrelin receptor antagonist injections have been shown to reduce operant responding for a sucrose solution (Landgren et al., 2011). Therefore, in the winter when ghrelin levels are low, a reduction in food-seeking, and potentially, consuming, behaviors would be predicted. "
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    ABSTRACT: Seasonal fluctuations in food availability show a tight association with seasonal variations in body weight and food intake. Seasonal variations in food intake, energy storage, and expenditure appear to be a widespread phenomenon suggesting they may have evolved in anticipation for changing environmental demands. These cycles appear to be driven by changes in external daylength acting on neuroendocrine pathways. A number of neuroendocrine pathways, two of which are the endocrine mechanisms underlying feeding and stress, appear to show seasonal changes in both their circulating levels and reactivity. As such, variation in the level or reactivity to these hormones may be crucial factors in the control of seasonal variations in food-seeking behaviors. The present review examines the relationship between feeding behavior and seasonal changes in circulating hormones. We hypothesize that seasonal changes in circulating levels of glucocorticoids and the feeding-related hormones ghrelin and leptin contribute to seasonal fluctuations in feeding-related behaviors. This review will focus on the seasonal circulating levels of these hormones as well as sensitivity to these hormones in the modulation of food-seeking behaviors.
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