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

Novel molecular targets are needed to develop new medications for the treatment of cocaine addiction. Here we investigated a role for glucagon-like peptide-1 (GLP-1) receptors in the reinstatement of cocaine-seeking behavior, an animal model of relapse. We showed that peripheral administration of th...

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Autores principales: Hernandez, Nicole S., Ige, Kelsey Y., Mietlicki-Baase, Elizabeth G., Molina-Castro, Gian Carlo, Turner, Christopher A., Hayes, Matthew R., Schmidt, Heath D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098066/
https://www.ncbi.nlm.nih.gov/pubmed/29497166
http://dx.doi.org/10.1038/s41386-018-0010-3
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author Hernandez, Nicole S.
Ige, Kelsey Y.
Mietlicki-Baase, Elizabeth G.
Molina-Castro, Gian Carlo
Turner, Christopher A.
Hayes, Matthew R.
Schmidt, Heath D.
author_facet Hernandez, Nicole S.
Ige, Kelsey Y.
Mietlicki-Baase, Elizabeth G.
Molina-Castro, Gian Carlo
Turner, Christopher A.
Hayes, Matthew R.
Schmidt, Heath D.
author_sort Hernandez, Nicole S.
collection PubMed
description Novel molecular targets are needed to develop new medications for the treatment of cocaine addiction. Here we investigated a role for glucagon-like peptide-1 (GLP-1) receptors in the reinstatement of cocaine-seeking behavior, an animal model of relapse. We showed that peripheral administration of the GLP-1 receptor agonist exendin-4 dose dependently reduced cocaine seeking in rats at doses that did not affect ad libitum food intake, meal patterns or body weight. We also demonstrated that systemic exendin-4 penetrated the brain where it putatively bound receptors on both neurons and astrocytes in the ventral tegmental area (VTA). The effects of systemic exendin-4 on cocaine reinstatement were attenuated in rats pretreated with intra-VTA infusions of the GLP-1 receptor antagonist exendin-(9–39), indicating that the suppressive effects of systemic exendin-4 on cocaine seeking were due, in part, to activation of GLP-1 receptors in the VTA. Consistent with these effects, infusions of exendin-4 directly into the VTA reduced cocaine seeking. Finally, extinction following cocaine self-administration was associated with decreased preproglucagon mRNA expression in the caudal brainstem. Thus, our study demonstrated a novel role for GLP-1 receptors in the reinstatement of cocaine-seeking behavior and identified behaviorally relevant doses of a GLP-1 receptor agonist that selectively reduced cocaine seeking and did not produce adverse effects.
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spelling pubmed-60980662019-09-01 Glucagon-like peptide-1 receptor activation in the ventral tegmental area attenuates cocaine seeking in rats Hernandez, Nicole S. Ige, Kelsey Y. Mietlicki-Baase, Elizabeth G. Molina-Castro, Gian Carlo Turner, Christopher A. Hayes, Matthew R. Schmidt, Heath D. Neuropsychopharmacology Article Novel molecular targets are needed to develop new medications for the treatment of cocaine addiction. Here we investigated a role for glucagon-like peptide-1 (GLP-1) receptors in the reinstatement of cocaine-seeking behavior, an animal model of relapse. We showed that peripheral administration of the GLP-1 receptor agonist exendin-4 dose dependently reduced cocaine seeking in rats at doses that did not affect ad libitum food intake, meal patterns or body weight. We also demonstrated that systemic exendin-4 penetrated the brain where it putatively bound receptors on both neurons and astrocytes in the ventral tegmental area (VTA). The effects of systemic exendin-4 on cocaine reinstatement were attenuated in rats pretreated with intra-VTA infusions of the GLP-1 receptor antagonist exendin-(9–39), indicating that the suppressive effects of systemic exendin-4 on cocaine seeking were due, in part, to activation of GLP-1 receptors in the VTA. Consistent with these effects, infusions of exendin-4 directly into the VTA reduced cocaine seeking. Finally, extinction following cocaine self-administration was associated with decreased preproglucagon mRNA expression in the caudal brainstem. Thus, our study demonstrated a novel role for GLP-1 receptors in the reinstatement of cocaine-seeking behavior and identified behaviorally relevant doses of a GLP-1 receptor agonist that selectively reduced cocaine seeking and did not produce adverse effects. Springer International Publishing 2018-02-14 2018-09 /pmc/articles/PMC6098066/ /pubmed/29497166 http://dx.doi.org/10.1038/s41386-018-0010-3 Text en © American College of Neuropsychopharmacology 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hernandez, Nicole S.
Ige, Kelsey Y.
Mietlicki-Baase, Elizabeth G.
Molina-Castro, Gian Carlo
Turner, Christopher A.
Hayes, Matthew R.
Schmidt, Heath D.
Glucagon-like peptide-1 receptor activation in the ventral tegmental area attenuates cocaine seeking in rats
title Glucagon-like peptide-1 receptor activation in the ventral tegmental area attenuates cocaine seeking in rats
title_full Glucagon-like peptide-1 receptor activation in the ventral tegmental area attenuates cocaine seeking in rats
title_fullStr Glucagon-like peptide-1 receptor activation in the ventral tegmental area attenuates cocaine seeking in rats
title_full_unstemmed Glucagon-like peptide-1 receptor activation in the ventral tegmental area attenuates cocaine seeking in rats
title_short Glucagon-like peptide-1 receptor activation in the ventral tegmental area attenuates cocaine seeking in rats
title_sort glucagon-like peptide-1 receptor activation in the ventral tegmental area attenuates cocaine seeking in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098066/
https://www.ncbi.nlm.nih.gov/pubmed/29497166
http://dx.doi.org/10.1038/s41386-018-0010-3
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