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

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
N S HernandezHeath D Schmidt

Abstract

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 ...Continue Reading

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Citations

Oct 4, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Yafang ZhangHeath D Schmidt
Jul 9, 2020·Addiction Biology·Antonio Jesús López-GamberoJuan Suárez
Mar 15, 2020·The Journal of Comparative Neurology·Devon L GrahamGregg D Stanwood
Feb 7, 2020·Current Pharmaceutical Design·Matthew M ClasenTerry L Davidson
Sep 21, 2018·Frontiers in Psychiatry·Ted M HsuMitchell F Roitman
Oct 13, 2020·Alcoholism, Clinical and Experimental Research·Tiarani N DixonZhi Yi Ong
Jan 17, 2021·Molecular Metabolism·Ruth HanssenMarc Tittgemeyer
Apr 2, 2019·Physiology & Behavior·N S Hernandez, H D Schmidt
Mar 21, 2021·Progress in Neuro-psychopharmacology & Biological Psychiatry·Eva Guerrero-HreinsPriya Sumithran
Dec 6, 2020·Progress in Neurobiology·Aimilia Lydia KalafateliElisabet Jerlhag
Apr 11, 2021·Physiology & Behavior·Elizabeth G Mietlicki-BaaseDerek Daniels
Apr 17, 2021·Neuropharmacology·Katherine M SerafineEric P Zorrilla
Nov 25, 2020·Behavioural Pharmacology·Joaquin E DoutonPatricia S Grigson
Jun 22, 2021·The Journal of Physiology·Orla R M WoodwardJo E Lewis

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Methods Mentioned

BETA
pharmacotherapies
PCR

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