Format

Send to

Choose Destination
Physiol Behav. 2015 Oct 1;149:262-8. doi: 10.1016/j.physbeh.2015.06.013. Epub 2015 Jun 11.

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

Author information

1
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark; Psychiatric Centre Copenhagen, University of Copenhagen, Denmark.
2
Neuroscience Graduate Program, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA; Neuroscience Program in Substance Abuse, Vanderbilt University Medical Center, Nashville, TN, USA.
3
Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee FL, USA.
4
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Denmark.
5
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA; Neuroscience Program in Substance Abuse, Vanderbilt University Medical Center, Nashville, TN, USA.
6
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark; Psychiatric Centre Copenhagen, University of Copenhagen, Denmark. Electronic address: a.fink-jensen@dadlnet.dk.

Abstract

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.

KEYWORDS:

Addiction; Cocaine; Dopamine; Exendin-4; GLP-1; Self-administration; c-Fos

PMID:
26072178
PMCID:
PMC4668599
DOI:
10.1016/j.physbeh.2015.06.013
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center