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glucagon-like peptide 1 (GLP-1) receptor agonist exendin-4 reduces cocaine self-administration in mice.

Title: The glucagon-like peptide 1 (GLP-1) receptor agonist exendin-4 reduces cocaine self-administration in mice.
Name(s): Sørensen, Gunnar, author
Reddy, India A, author
Weikop, Pia, author
Graham, Devon L, author
Stanwood, Gregg D, author
Wortwein, Gitta, author
Galli, Aurelio, author
Fink-Jensen, Anders, author
Type of Resource: text
Genre: Journal Article
Date Issued: 2015-10-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Glucagon-like peptide 1 (GLP-1) analogues are used for the treatment of type 2 diabetes. The ability of the GLP-1 system to decrease food intake in rodents has been well described and parallels results from clinical trials. GLP-1 receptors are expressed in the brain, including within the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Dopaminergic neurons in the VTA project to the NAc, and these neurons play a pivotal role in the rewarding effects of drugs of abuse. Based on the anatomical distribution of GLP-1 receptors in the brain and the well-established effects of GLP-1 on food reward, we decided to investigate the effect of the GLP-1 analogue exendin-4 on cocaine- and dopamine D1-receptor agonist-induced hyperlocomotion, on acute and chronic cocaine self-administration, on cocaine-induced striatal dopamine release in mice and on cocaine-induced c-fos activation. Here, we report that GLP-1 receptor stimulation reduces acute and chronic cocaine self-administration and attenuates cocaine-induced hyperlocomotion. In addition, we show that peripheral administration of exendin-4 reduces cocaine-induced elevation of striatal dopamine levels and striatal c-fos expression implicating central GLP-1 receptors in these responses. The present results demonstrate that the GLP-1 system modulates cocaine's effects on behavior and dopamine homeostasis, indicating that the GLP-1 receptor may be a novel target for the pharmacological treatment of drug addiction.
Identifier: FSU_pmch_26072178 (IID), 10.1016/j.physbeh.2015.06.013 (DOI), PMC4668599 (PMCID), 26072178 (RID), 26072178 (EID), S0031-9384(15)00349-2 (PII)
Keywords: Addiction, Cocaine, Dopamine, Exendin-4, GLP-1, Self-administration, C-Fos
Grant Number: DA035588, T32 GM07347, T32 GM007347, DA036940, F30 DA036940, R21 DA035588
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at
Subject(s): Analysis of Variance
Cocaine/administration & dosage
Corpus Striatum/drug effects
Corpus Striatum/metabolism
Dopamine Agonists/toxicity
Dopamine Uptake Inhibitors/administration & dosage
Dose-Response Relationship, Drug
Exploratory Behavior/drug effects
Gene Expression Regulation/drug effects
Hyperkinesis/chemically induced
Hypoglycemic Agents/pharmacology
Motor Activity/drug effects
Proto-Oncogene Proteins c-fos/genetics
Proto-Oncogene Proteins c-fos/metabolism
Self Administration
Time Factors
Persistent Link to This Record:
Owner Institution: FSU
Is Part Of: Physiology & behavior.
Issue: vol. 149

Choose the citation style.
Sørensen, G., Reddy, I. A., Weikop, P., Graham, D. L., Stanwood, G. D., Wortwein, G., … Fink-Jensen, A. (2015). The glucagon-like peptide 1 (GLP-1) receptor agonist exendin-4 reduces cocaine self-administration in mice. Physiology & Behavior. Retrieved from