scholarly journals Glucagon-Like Peptide-1 (GLP-1) and 5-Hydroxytryptamine 2c (5-HT2c) Receptor Agonists in the Ventral Tegmental Area (VTA) Inhibit Ghrelin-Stimulated Appetitive Reward

2019 ◽  
Vol 20 (4) ◽  
pp. 889 ◽  
Author(s):  
Erin Howell ◽  
Hannah Baumgartner ◽  
Lia Zallar ◽  
Joaquín Selva ◽  
Liv Engel ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Receptor Agonist ◽  
Food Reinforcement ◽  
Progressive Ratio ◽  
Sprague Dawley ◽  
Operant Responding ◽  
Orexigenic Peptide ◽  
Glucagon Like Peptide ◽  
Ventral Tegmental ◽  
Glucagon Like Peptide 1

Current literature indicates that the orexigenic peptide ghrelin increases appetitive motivation via signaling in the mesolimbic reward system. Another gastric peptide, glucagon-like peptide-1 (GLP-1), and the neurotransmitter 5-hydroxytryptamine (5-HT), are both known to suppress operant responding for food by acting on key mesolimbic nuclei, including the ventral tegmental area (VTA). In order to investigate the interaction effects of ghrelin, GLP-1, and 5-HT within the VTA, we measured operant responding for sucrose pellets after the administration of ghrelin, the GLP-1 receptor agonist exendin-4 (Ex-4), and the 5-HT2c receptor agonist Ro60-0175 in male Sprague-Dawley rats. Following training on a progressive ratio 3 (PR3) schedule, animals were first injected with ghrelin into the VTA at doses of 3 to 300 pmol. In subsequent testing, separate rats were administered intraperitoneal (IP) Ex-4 (0.1–1.0 µg/kg) or VTA Ex-4 (0.01–0.1 µg) paired with 300 pmol ghrelin. In a final group of rats, the 5-HT2c agonist Ro60-0175 was injected IP (0.25–1.0 mg/kg) or into the VTA (1.5–3.0 µg), and under both conditions paired with 300 pmol ghrelin delivered into the VTA. Our results indicated that ghrelin administration increased operant responding for food reward and that this effect was attenuated by IP and VTA Ex-4 pretreatment as well as pre-administration of IP or VTA Ro60-0175. These data provide compelling evidence that mesolimbic GLP-1 and serotonergic circuitry interact with the ghrelinergic system to suppress ghrelin’s effects on the mediation of food reinforcement.

scholarly journals Glucagon-Like Peptide-1 Receptor Agonist Liraglutide Ameliorates the Development of Periodontitis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Noritaka Sawada ◽  
Kei Adachi ◽  
Nobuhisa Nakamura ◽  
Megumi Miyabe ◽  
Mizuho Ito ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Alveolar Bone ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Sprague Dawley ◽  
Gene Expressions ◽  
Second Molar ◽  
Sd Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Periodontitis is one of the diabetic complications due to its high morbidity and severity in patients with diabetes. The prevention of periodontitis is especially important in diabetic patients because the relationship between diabetes and periodontitis is bidirectional. Here, we evaluated the impacts of glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on the amelioration of periodontitis. Five-wk-old Male Sprague–Dawley (SD) rats ( n = 30 ) were divided into 3 groups: normal, periodontitis, and periodontitis with liraglutide treatment groups. Periodontitis was induced by ligature around the maxillary second molar in SD rats. Half of the rats were administered liraglutide for 2 weeks. Periodontitis was evaluated by histological staining, gene expressions of inflammatory cytokines in gingiva, and microcomputed tomography. Periodontitis increased inflammatory cell infiltration, macrophage accumulation, and gene expressions of tumor necrosis factor-α and inducible nitric oxide synthase in the gingiva, all of which were ameliorated by liraglutide. Liraglutide decreased M1 macrophages but did not affect M2 macrophages in periodontitis. Moreover, ligature-induced alveolar bone resorption was ameliorated by liraglutide. Liraglutide treatment also reduced osteoclasts on the alveolar bone surface. These results highlight the beyond glucose-lowering effects of liraglutide on the treatment of periodontitis.

scholarly journals The food intake-suppressive effects of glucagon-like peptide-1 receptor signaling in the ventral tegmental area are mediated by AMPA/kainate receptors

2013 ◽  
Vol 305 (11) ◽  
pp. E1367-E1374 ◽  
Author(s):  
Elizabeth G. Mietlicki-Baase ◽  
Pavel I. Ortinski ◽  
Laura E. Rupprecht ◽  
Diana R. Olivos ◽  
Amber L. Alhadeff ◽  
...  
Keyword(s):  
Food Intake ◽  
Ventral Tegmental Area ◽  
Dopamine Neurons ◽  
Kainate Receptors ◽  
System Control ◽  
Receptor Signaling ◽  
Palatable Food ◽  
Glucagon Like Peptide ◽  
Ventral Tegmental ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 receptor (GLP-1R) activation in the ventral tegmental area (VTA) is physiologically relevant for the control of palatable food intake. Here, we tested whether the food intake-suppressive effects of VTA GLP-1R activation are mediated by glutamatergic signaling within the VTA. Intra-VTA injections of the GLP-1R agonist exendin-4 (Ex-4) reduced palatable high-fat food intake in rats primarily by reducing meal size; these effects were mediated in part via glutamatergic AMPA/kainate but not NMDA receptor signaling. Additional behavioral data indicated that GLP-1R expressed specifically within the VTA can partially mediate the intake- and body weight-suppressive effects of systemically administered Ex-4, offering the intriguing possibility that this receptor population may be clinically relevant for food intake control. Intra-VTA Ex-4 rapidly increased tyrosine hydroxylase levels within the VTA, suggesting that GLP-1R activation modulates VTA dopaminergic signaling. Further evidence for this hypothesis was provided by electrophysiological data showing that Ex-4 increased the frequency of AMPA-mediated currents and reduced the paired/pulse ratio in VTA dopamine neurons. Together, these data provide novel mechanisms by which GLP-1R agonists in the mesolimbic reward system control for palatable food intake.

scholarly journals Glucagon-Like Peptide-1 Receptor Activation in the Ventral Tegmental Area Decreases the Reinforcing Efficacy of Cocaine

2015 ◽  
Vol 41 (7) ◽  
pp. 1917-1928 ◽  
Author(s):  
Heath D Schmidt ◽  
Elizabeth G Mietlicki-Baase ◽  
Kelsey Y Ige ◽  
John J Maurer ◽  
David J Reiner ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Receptor Activation ◽  
Reinforcing Efficacy ◽  
Glucagon Like Peptide ◽  
Ventral Tegmental ◽  
Glucagon Like Peptide 1

scholarly journals Glucagon-like peptide-1 receptor activation in the ventral tegmental area attenuates cocaine seeking in rats

2018 ◽  
Vol 43 (10) ◽  
pp. 2000-2008 ◽  
Author(s):  
Nicole S. Hernandez ◽  
Kelsey Y. Ige ◽  
Elizabeth G. Mietlicki-Baase ◽  
Gian Carlo Molina-Castro ◽  
Christopher A. Turner ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Receptor Activation ◽  
Cocaine Seeking ◽  
Glucagon Like Peptide ◽  
Ventral Tegmental ◽  
Glucagon Like Peptide 1

scholarly journals Glucagon-Like Peptide-1 Receptor Agonist, Liraglutide, Attenuated Diabetic Retinal Edema in Spontaneously Diabetic Torii Fatty Rats

2021 ◽  
Author(s):  
Kazuho Inoue ◽  
Shohei Yamada ◽  
Seiko Hoshino ◽  
Minoru Watanabe ◽  
Kenjiro Kimura ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Glucose ◽  
Receptor Agonist ◽  
Vehicle Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Retinal Edema ◽  
Monocyte Chemoattractant Protein 1 ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Background: This study aims to investigate the effect of the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) liraglutide on retinal edema as compared with insulin and hydralazine using an animal model of type 2 diabetes with obesity, hypertension, and hyperlipidemia.Methods: Male spontaneously diabetic Torii (SDT) fatty rats at 8 weeks of age were randomly assigned to three groups: the liraglutide group (SDT-lira, n = 6) received a subcutaneous injection of liraglutide from the age of 8 to 16 weeks, the SDT-ins-hyd group (n = 6) was provided both insulin against hyperglycemia and hydralazine against hypertension to match levels of both blood glucose and blood pressure to those of the liraglutide group, and the control group of SDT fatty rats (SDT-vehicle, n = 7) and a nondiabetic control group of Sprague–Dawley rats (SD, n = 7) were injected with vehicle only. Both eyeballs of all groups were collected at the age of 16 weeks.Results: Retinal thickness, which was found in the SDT-vehicle group, was significantly prevented to similar levels in both the SDT-lira and SDT-ins-hyd groups. Immunohistological analysis revealed that GLP-1 receptor was not expressed in the retina of all rats. The ocular protein expression of monocyte chemoattractant protein-1, which causes a proinflammatory situation, was significantly upregulated in all SDT fatty rats as compared to SD rats, but the expression levels were similar between all SDT fatty rats. With regard to neovascularization in the eyes, there were no significant differences in protein expressions of vascular endothelial growth factor, CD31, or endothelial nitric oxide synthase in all rats.Conclusions: The present study indicates that liraglutide prevents retinal thickening, dependent on blood glucose and blood pressure levels in SDT fatty rats without ocular neovascularization. However, the effects did not improve the ocular proinflammatory state.

Dulaglutide, a glucagon-like peptide-1 receptor agonist: in the search for survival molecule

2020 ◽  
Vol 9 (2) ◽  
pp. 49-58
Author(s):  
A.S. Ametov ◽  
◽  
A.O. Nevolnikova ◽  
E.A. Tertychnaya ◽  
O.A. Mishra ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Liraglutide, a glucagon-like peptide-1 receptor agonist, improves bone mass and architecture in ovariectomised mice

2014 ◽  
Author(s):  
Marie Pereira ◽  
Jeshmi Jeyabalan ◽  
Camilla Sofie Jorgensen ◽  
Mark Cleasby ◽  
Mark Hopkinson ◽  
...  
Keyword(s):  
Bone Mass ◽  
Receptor Agonist ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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