Effects of 18-methoxycoronaridine on ghrelin-induced increases in sucrose intake and accumbal dopamine overflow in female rats

McCallum, Sarah E.; Taraschenko, Olga; Hathaway, Ethan R.; Vincent, Melanie Y.; Glick, Stanley D.

doi:10.1007/s00213-010-2132-0

Cited by 20 publications

(18 citation statements)

References 32 publications

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“…Further, peripheral administration of ghrelin increased the intake and preference of sucrose in rats. Supportively, it was recently shown that ghrelin (administered centrally as well as peripherally) increases whereas GHS-R1A antagonism suppresses the motivation to consume sucrose [37] and that central grelin administration increase the intake of sucrose in rats [38]. Given that the orexigenic peptide, ghrelin, regulates energy balance [8], the reduced sucrose intake may be related to its caloric content.…”

Section: Discussionmentioning

confidence: 97%

The Ghrelin Signalling System Is Involved in the Consumption of Sweets

et al. 2011

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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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Section: Discussionmentioning

confidence: 97%

The Ghrelin Signalling System Is Involved in the Consumption of Sweets

et al. 2011

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“…In terms of behavior, it is clear that ghrelin alters the rewarding properties associated with food and drug reinforcers (Perello et al, 2010, Jerlhag et al, 2009, 2010, McCallum et al, 2011, Skibicka 2011, 2012). For example, ghrelin administration enhances the rewarding properties of high fat diet while ghrelin receptor antagonists abolish this effect (Perello et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Recent work implicates a necessity for ghrelin signaling in a variety of rewarding behaviors including food, alcohol and psychostimulant reinforcement (Perello et al, 2010, Jerlhag et al, 2009, 2010, McCallum et al, 2011, Skibicka 2011, 2012). The mechanism of ghrelin action in the context of reward behavior likely occurs through activation of the ghrelin receptor (GHSR) (Jerlhag et al, 2009) within tegmental and cholinergic signaling systems which activate brain reward circuitry (Jerlhag et al, 2006, 2007, Skibicka et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

GOAT induced ghrelin acylation regulates hedonic feeding

Davis

Perelló

Choi

et al. 2012

Hormones and Behavior

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Ghrelin is an orexigenic hormone that regulates homeostatic and reward-related feeding behavior. Recent evidence indicates that acylation of ghrelin by the gut enzyme ghrelin O-acyl transferase (GOAT) is necessary to render ghrelin maximally active within its target tissues. Here we tested the hypothesis that GOAT activity modulates food motivation and food hedonics using behavioral pharmacology and mutant mice deficient for GOAT and the ghrelin receptor (GHSR). We evaluated operant responding following pharmacological administration of acyl-ghrelin and assessed the necessity of endogenous GOAT activity for operant responding in GOAT and GHSR-null mice. Hedonic-based feeding behavior also was examined in GOAT-KO and GHSR-null mice using a “Dessert Effect” protocol in which the intake of a palatable high fat diet “dessert” was assessed in calorically-sated mice. Pharmacological administration of acyl-ghrelin augmented operant responding; notably, this effect was dependent on intact GHSR signaling. GOAT-KO mice displayed attenuated operant responding and decreased hedonic feeding relative to controls. These behavioral results correlated with decreased expression of the orexin-1 receptor in reward-related brain regions in GOAT-KO mice. In summary, the ability of ghrelin to stimulate food motivation is dependent on intact GHSR signaling and modified by endogenous GOAT activity. Furthermore, GOAT activity is required for hedonic feeding behavior, an effect potentially mediated by forebrain orexin signaling. These data highlight the significance of the GOAT-ghrelin system for the mediation of food motivation and hedonic feeding.

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“…Plasma acylated-ghrelin level was positively correlated with carbohydrate consumption, while inversely correlated with fat intake in rat (Beck et al 2002). Peripheral and central acylated-ghrelin injection stimulated dopamine release in NAc, accompanied by increased sucrose consumption (Landgren et al 2011, McCallum et al 2011. In addition, a populationbased genetic study in humans showed that pro-ghrelin gene (GHRL) haplotype was associated with sucrose preference (Landgren et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Ghrelin O-acyltransferase knockout mice show resistance to obesity when fed high-sucrose diet

Kouno

Akiyama

Ito

et al. 2015

Journal of Endocrinology

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Ghrelin is an appetite-stimulating hormone secreted from stomach. Since the discovery that acylation of the serine-3 residue by ghrelin O-acyltransferase (GOAT) is essential for exerting its functions, GOAT has been regarded as an therapeutic target for attenuating appetite, and thus for the treatment of obesity and diabetes. However, contrary to the expectations, GOAT-knockout (KO) mice have not shown meaningful body weight reduction, under high-fat diet. Here, in this study, we sought to determine whether GOAT has a role in body weight regulation and glucose metabolism with a focus on dietary sucrose, because macronutrient composition of diet is important for appetite regulation. We found that peripherally administered acylated-ghrelin, but not unacylated one, stimulated sucrose consumption in a two-bottle-drinking test. The role of acylated-ghrelin in sucrose preference was further supported by the finding that GOAT KO mice consumed less sucrose solution compared with WT littermates. Then, we investigated the effect of dietary composition of sucrose on food intake and body weight in GOAT KO and WT mice. As a result, when fed on high-fat diet, food intake and body weight were similar between GOAT KO and WT mice. However, when fed on high-fat, high-sucrose diet, GOAT KO mice showed significantly reduced food intake and marked resistance to obesity, leading to amelioration of glucose metabolism. These results suggest that blockade of acylated-ghrelin production offers therapeutic potential for obesity and metabolic disorders caused by overeating of palatable food.

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Effects of 18-methoxycoronaridine on ghrelin-induced increases in sucrose intake and accumbal dopamine overflow in female rats

Cited by 20 publications

References 32 publications

The Ghrelin Signalling System Is Involved in the Consumption of Sweets

The Ghrelin Signalling System Is Involved in the Consumption of Sweets

GOAT induced ghrelin acylation regulates hedonic feeding

Ghrelin O-acyltransferase knockout mice show resistance to obesity when fed high-sucrose diet

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