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Role of ghrelin in food reward: impact of ghrelin on sucrose self-administration and mesolimbic dopamine and acetylcholine receptor gene expression.

Skibicka KP, Hansson C, Egecioglu E, Dickson SL - Addict Biol (2011)

Bottom Line: Utilizing the GHS-R1A antagonist JMV2959, we demonstrated that blockade of GHS-R1A signaling significantly decreased operant responding for sucrose.We further investigated ghrelin's effects on key mesolimbic reward nodes, the ventral tegmental area (VTA) and nucleus accumbens (NAcc), by evaluating the effects of chronic central ghrelin treatment on the expression of genes encoding major reward neurotransmitter receptors, namely dopamine and acetylcholine.Ghrelin treatment was associated with an increased dopamine receptor D5 and acetylcholine receptor nAChRβ2 gene expression in the VTA and decreased expression of D1, D3, D5 and nAChRα3 in the NAcc.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden. karolina.skibicka@neuro.gu.se

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Peripheral delivery of a ghrelin receptor antagonist, JMV2959. decreases the motivation to obtain palatable food in a PR ratio operant conditioning model. The number of responses on the active lever (a) and the number of 45 mg sucrose rewards obtained (b) are significantly decreased by IP JMV2959 injection for the 120-minute period of operant testing. Data represent the mean ± SEM, n = 13, *P < 0.05, **P < 0.005 from vehicle, post hoc Tukey analysis
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fig03: Peripheral delivery of a ghrelin receptor antagonist, JMV2959. decreases the motivation to obtain palatable food in a PR ratio operant conditioning model. The number of responses on the active lever (a) and the number of 45 mg sucrose rewards obtained (b) are significantly decreased by IP JMV2959 injection for the 120-minute period of operant testing. Data represent the mean ± SEM, n = 13, *P < 0.05, **P < 0.005 from vehicle, post hoc Tukey analysis

Mentions: Next, we explored the effects of pharmacological blockade of GHS-R1A on sucrose reward efficacy. Thus, sucrose self-administration in a progressive response schedule was examined in the overnight food-restricted rats to ensure high levels of endogenous circulating ghrelin 20 minutes after IP injection of vehicle or 1 mg/kg or 3 mg/kg of JMV2959, a GHS-R1A antagonist. All of the measures of operant behavior were significantly decreased in the rats after peripheral injection of JMV2959 [active lever: five minutes F(2, 24) = 11.53 P < 0.0005, 120 minutes F(2, 24) = 11.27, P < 0.001; rewards earned: five minutes F(2, 24) = 23.39 P < 0.0005, 120 minutes F(2, 24) = 9.26, P < 0.001 and break point at 120: F(2, 24) = 5.98, P < 0.01 (45.31 ± 6.45, 42.08 ± 5.80, 30.0 ± 5.89 for vehicle, 1 mg/kg and 3 mg/kg JMV2959, respectively)]. Post hoc analysis revealed that the main effect was driven by the 3 mg/kg dose (Fig. 3a,b). To determine the role of the central ghrelin receptor in sucrose reward efficacy, a similar study was performed in which vehicle or JMV2959 (5 µg or 10 µg) was administered to the third ventricle 20 minutes before the operant measurements. All of the aforementioned measures of operant behavior were significantly decreased in the rats after acute third ventricle infusion of both doses of JMV2959 (Fig. 4a,b). The observed effect was immediate as post hoc analysis revealed significant differences among the treatment groups only after 10 minutes of activity in the operant chamber that were maintained throughout the testing period [active lever: 10 minutes F(2, 24) = 10.16, P < 0.0005, 30 minutes F(2, 24) = 11.48, P < 0.0005, 60 minutes F(2, 24) = 9.11, P < 0.001, 90 minutes F(2, 24) = 8.30, P < 0.001, 120 minutes F(2, 24) = 4.95, P < 0.05; rewards earned: 10 minutes F(2, 24) = 21.23, P < 0.0001, 30 minutes F(2, 24) = 25.08, P < 0.0001, 60 minutes F(2, 24) = 19.24, P < 0.0001, 90 minutes F(2, 24) = 20.04, P < 0.0001, 120 minutes F(2, 24) = 5.44, P < 0.01; and break point: F(2, 24) = 3.78, P < 0.05 (51.4 ± 8.58, 38.13 ± 5.07, 33.67 ± 5.21 for vehicle, 5 µg and 10 µg JMV2959, respectively)].


Role of ghrelin in food reward: impact of ghrelin on sucrose self-administration and mesolimbic dopamine and acetylcholine receptor gene expression.

Skibicka KP, Hansson C, Egecioglu E, Dickson SL - Addict Biol (2011)

Peripheral delivery of a ghrelin receptor antagonist, JMV2959. decreases the motivation to obtain palatable food in a PR ratio operant conditioning model. The number of responses on the active lever (a) and the number of 45 mg sucrose rewards obtained (b) are significantly decreased by IP JMV2959 injection for the 120-minute period of operant testing. Data represent the mean ± SEM, n = 13, *P < 0.05, **P < 0.005 from vehicle, post hoc Tukey analysis
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3298643&req=5

fig03: Peripheral delivery of a ghrelin receptor antagonist, JMV2959. decreases the motivation to obtain palatable food in a PR ratio operant conditioning model. The number of responses on the active lever (a) and the number of 45 mg sucrose rewards obtained (b) are significantly decreased by IP JMV2959 injection for the 120-minute period of operant testing. Data represent the mean ± SEM, n = 13, *P < 0.05, **P < 0.005 from vehicle, post hoc Tukey analysis
Mentions: Next, we explored the effects of pharmacological blockade of GHS-R1A on sucrose reward efficacy. Thus, sucrose self-administration in a progressive response schedule was examined in the overnight food-restricted rats to ensure high levels of endogenous circulating ghrelin 20 minutes after IP injection of vehicle or 1 mg/kg or 3 mg/kg of JMV2959, a GHS-R1A antagonist. All of the measures of operant behavior were significantly decreased in the rats after peripheral injection of JMV2959 [active lever: five minutes F(2, 24) = 11.53 P < 0.0005, 120 minutes F(2, 24) = 11.27, P < 0.001; rewards earned: five minutes F(2, 24) = 23.39 P < 0.0005, 120 minutes F(2, 24) = 9.26, P < 0.001 and break point at 120: F(2, 24) = 5.98, P < 0.01 (45.31 ± 6.45, 42.08 ± 5.80, 30.0 ± 5.89 for vehicle, 1 mg/kg and 3 mg/kg JMV2959, respectively)]. Post hoc analysis revealed that the main effect was driven by the 3 mg/kg dose (Fig. 3a,b). To determine the role of the central ghrelin receptor in sucrose reward efficacy, a similar study was performed in which vehicle or JMV2959 (5 µg or 10 µg) was administered to the third ventricle 20 minutes before the operant measurements. All of the aforementioned measures of operant behavior were significantly decreased in the rats after acute third ventricle infusion of both doses of JMV2959 (Fig. 4a,b). The observed effect was immediate as post hoc analysis revealed significant differences among the treatment groups only after 10 minutes of activity in the operant chamber that were maintained throughout the testing period [active lever: 10 minutes F(2, 24) = 10.16, P < 0.0005, 30 minutes F(2, 24) = 11.48, P < 0.0005, 60 minutes F(2, 24) = 9.11, P < 0.001, 90 minutes F(2, 24) = 8.30, P < 0.001, 120 minutes F(2, 24) = 4.95, P < 0.05; rewards earned: 10 minutes F(2, 24) = 21.23, P < 0.0001, 30 minutes F(2, 24) = 25.08, P < 0.0001, 60 minutes F(2, 24) = 19.24, P < 0.0001, 90 minutes F(2, 24) = 20.04, P < 0.0001, 120 minutes F(2, 24) = 5.44, P < 0.01; and break point: F(2, 24) = 3.78, P < 0.05 (51.4 ± 8.58, 38.13 ± 5.07, 33.67 ± 5.21 for vehicle, 5 µg and 10 µg JMV2959, respectively)].

Bottom Line: Utilizing the GHS-R1A antagonist JMV2959, we demonstrated that blockade of GHS-R1A signaling significantly decreased operant responding for sucrose.We further investigated ghrelin's effects on key mesolimbic reward nodes, the ventral tegmental area (VTA) and nucleus accumbens (NAcc), by evaluating the effects of chronic central ghrelin treatment on the expression of genes encoding major reward neurotransmitter receptors, namely dopamine and acetylcholine.Ghrelin treatment was associated with an increased dopamine receptor D5 and acetylcholine receptor nAChRβ2 gene expression in the VTA and decreased expression of D1, D3, D5 and nAChRα3 in the NAcc.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden. karolina.skibicka@neuro.gu.se

Show MeSH
Related in: MedlinePlus