Brain region specific glucagon-like peptide-1 receptors regulate alcohol-induced behaviors in rodents

Feb 17, 2019Psychoneuroendocrinology

Glucagon-like peptide-1 receptors in specific brain areas influence alcohol-related behaviors in rodents

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Bilateral infusion of the GLP-1R agonist exendin-4 (Ex4) into the NAc shell significantly decreases alcohol intake and blocks alcohol-induced locomotor stimulation.

Ex4 infusion into the NAc shell blocks both alcohol-induced locomotor stimulation and memory of alcohol reward in mice.
Alcohol intake is reduced in rats consuming high amounts of alcohol for 12 weeks following Ex4 infusion into the NAc shell.
GLP-1 receptor expression in the NAc is higher in rats that consume more alcohol compared to those that consume less.
Ex4 infusion into the anterior ventral tegmental area (aVTA) does not affect alcohol-induced behaviors.
Ex4 in the posterior ventral tegmental area (pVTA) prevents locomotor stimulation but has no impact on alcohol memory or intake.
Intra-LDTg-Ex4 reduces alcohol intake and locomotor stimulation but does not influence memory of alcohol reward.

AI simplified

Glucagon-like peptide 1 (GLP-1), an incretin hormone that reduces food intake, was recently established as a novel regulator of alcohol-mediated behaviors. Clinically available analogues pass freely into the brain, but the mechanisms underlying GLP-1-modulated alcohol reward remains largely unclear. GLP-1 receptors (GLP-1R) are expressed throughout the nuclei of importance for acute and chronic effects of alcohol, such as the laterodorsal tegmental area (LDTg), the ventral tegmental area (VTA) and the nucleus accumbens (NAc). We therefore evaluated the effects of bilateral infusion of the GLP-1R agonist exendin-4 (Ex4) into NAc shell, anterior (aVTA), posterior (pVTA) or LDTg on the acute alcohol-induced locomotor stimulation and memory of alcohol reward in the conditioned place preference (CPP) model in mice, as well as on alcohol intake in rats consuming high amounts of alcohol for 12 weeks. Ex4 into the NAc shell blocks alcohol-induced locomotor stimulation and memory of alcohol reward as well as decreases alcohol intake. The GLP-1R expression in NAc is elevated in high compared to low alcohol-consuming rats. On the contrary, GLP-1R activation in the aVTA does not modulate alcohol-induced behaviors. Ex4 into the pVTA prevents alcohol-induced locomotor simulation, but does neither modulate CPP-dependent alcohol memory nor alcohol intake. Intra-LDTg-Ex4 attenuates alcohol-induced locomotor stimulation and reduces alcohol intake, but does not affect memory of alcohol reward. Collectively, these data provide additional knowledge of the functional role of GLP-1R in reward-related areas for alcohol-mediated behaviors and further support GLP-1R as a potential treatment target for alcohol use disorder.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Brain region specific glucagon-like peptide-1 receptors regulate alcohol-induced behaviors in rodents

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief