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

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...

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Autores principales: Howell, Erin, Baumgartner, Hannah M., Zallar, Lia J., Selva, Joaquín A., Engel, Liv, Currie, Paul J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412472/
https://www.ncbi.nlm.nih.gov/pubmed/30791361
http://dx.doi.org/10.3390/ijms20040889
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author Howell, Erin
Baumgartner, Hannah M.
Zallar, Lia J.
Selva, Joaquín A.
Engel, Liv
Currie, Paul J.
author_facet Howell, Erin
Baumgartner, Hannah M.
Zallar, Lia J.
Selva, Joaquín A.
Engel, Liv
Currie, Paul J.
author_sort Howell, Erin
collection PubMed
description 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-HT(2c) 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-HT(2c) 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.
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spelling pubmed-64124722019-04-05 Glucagon-Like Peptide-1 (GLP-1) and 5-Hydroxytryptamine 2c (5-HT(2c)) Receptor Agonists in the Ventral Tegmental Area (VTA) Inhibit Ghrelin-Stimulated Appetitive Reward Howell, Erin Baumgartner, Hannah M. Zallar, Lia J. Selva, Joaquín A. Engel, Liv Currie, Paul J. Int J Mol Sci Article 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-HT(2c) 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-HT(2c) 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. MDPI 2019-02-19 /pmc/articles/PMC6412472/ /pubmed/30791361 http://dx.doi.org/10.3390/ijms20040889 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Howell, Erin
Baumgartner, Hannah M.
Zallar, Lia J.
Selva, Joaquín A.
Engel, Liv
Currie, Paul J.
Glucagon-Like Peptide-1 (GLP-1) and 5-Hydroxytryptamine 2c (5-HT(2c)) Receptor Agonists in the Ventral Tegmental Area (VTA) Inhibit Ghrelin-Stimulated Appetitive Reward
title Glucagon-Like Peptide-1 (GLP-1) and 5-Hydroxytryptamine 2c (5-HT(2c)) Receptor Agonists in the Ventral Tegmental Area (VTA) Inhibit Ghrelin-Stimulated Appetitive Reward
title_full Glucagon-Like Peptide-1 (GLP-1) and 5-Hydroxytryptamine 2c (5-HT(2c)) Receptor Agonists in the Ventral Tegmental Area (VTA) Inhibit Ghrelin-Stimulated Appetitive Reward
title_fullStr Glucagon-Like Peptide-1 (GLP-1) and 5-Hydroxytryptamine 2c (5-HT(2c)) Receptor Agonists in the Ventral Tegmental Area (VTA) Inhibit Ghrelin-Stimulated Appetitive Reward
title_full_unstemmed Glucagon-Like Peptide-1 (GLP-1) and 5-Hydroxytryptamine 2c (5-HT(2c)) Receptor Agonists in the Ventral Tegmental Area (VTA) Inhibit Ghrelin-Stimulated Appetitive Reward
title_short Glucagon-Like Peptide-1 (GLP-1) and 5-Hydroxytryptamine 2c (5-HT(2c)) Receptor Agonists in the Ventral Tegmental Area (VTA) Inhibit Ghrelin-Stimulated Appetitive Reward
title_sort glucagon-like peptide-1 (glp-1) and 5-hydroxytryptamine 2c (5-ht(2c)) receptor agonists in the ventral tegmental area (vta) inhibit ghrelin-stimulated appetitive reward
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412472/
https://www.ncbi.nlm.nih.gov/pubmed/30791361
http://dx.doi.org/10.3390/ijms20040889
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