Back to Search
Start Over
Glucagon-like peptide-1 receptor activation in the ventral tegmental area attenuates cocaine seeking in rats.
- Source :
-
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2018 Sep; Vol. 43 (10), pp. 2000-2008. Date of Electronic Publication: 2018 Feb 14. - Publication Year :
- 2018
-
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 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.
- Subjects :
- Animals
Astrocytes drug effects
Brain metabolism
Cocaine-Related Disorders psychology
Conditioning, Operant drug effects
Dose-Response Relationship, Drug
Exenatide administration & dosage
Exenatide pharmacokinetics
Male
Neurons drug effects
Proglucagon biosynthesis
Proglucagon genetics
Rats
Rats, Sprague-Dawley
Recurrence
Solitary Nucleus drug effects
Solitary Nucleus metabolism
Anti-Obesity Agents therapeutic use
Cocaine-Related Disorders drug therapy
Drug-Seeking Behavior drug effects
Exenatide therapeutic use
Glucagon-Like Peptide-1 Receptor agonists
Glucagon-Like Peptide-1 Receptor metabolism
Ventral Tegmental Area drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1740-634X
- Volume :
- 43
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 29497166
- Full Text :
- https://doi.org/10.1038/s41386-018-0010-3