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Glucagon-like peptide-1 receptors within the nucleus of the solitary tract regulate alcohol-mediated behaviors in rodents

Artikel i vetenskaplig tidskrift
Författare Daniel Vallöf
Jesper Vestlund
Elisabeth Jerlhag
Publicerad i Neuropharmacology
Volym 149
Sidor 124-132
ISSN 0028-3908
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi
Sidor 124-132
Språk en
Länkar dx.doi.org/10.1016/j.neuropharm.201...
Ämnesord Alcohol use disorder, Dopamine, Reward, Gut-brain axis, ventral tegmental area, glp-1 receptor, food-intake, agonist exendin-4, rat-brain, messenger-rna, neurons, preproglucagon, accumbens, activation
Ämneskategorier Farmakologi

Sammanfattning

The ability of glucagon-like peptide-1 (GLP-1) to reduce food intake involves activation of GLP-1 receptors (GLP-1R) in the nucleus of the solitary tract (NTS). It has also been demonstrated that systemic administration of GLP-1R agonists attenuates alcohol-mediated behaviors via, to date, unknown mechanisms. Therefore, we evaluated the effects of NTS-GLP-1R activation by exendin-4 (Ex4) on alcohol-induced locomotor stimulation, accumbal dopamine release and memory of alcohol reward in the conditioned place preference (CPP) model in mice. Moreover, the ability of Ex4 infusion into the NTS on alcohol intake was explored in rats. Ex4 into the NTS inhibits the acute effects of alcohol as measured by alcohol-induced locomotor stimulation, accumbal dopamine release and the memory consolidation of alcohol reward in the CPP paradigm. In addition, NTS-Ex4 dose-dependently decreases alcohol intake in rats consuming alcohol for 12 weeks. Pharmacological suppression of GLP-1R in the NTS prevents the ability of systemic Ex4 to block the alcohol-induced locomotor stimulation in mice. These data add a functional role of GLP-1R within the NTS, involving alcohol-related behaviors. In addition, they may provide insight into the GLP-1R containing brain areas that modulate the ability of GLP-1R agonists to reduce alcohol reinforcement. Collectively, this further supports GLP-1R as potential treatment targets for alcohol use disorder.

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http://gu.se/forskning/publikation/?publicationId=280172
Utskriftsdatum: 2019-11-22