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

NEUROPHARMACOLOGY

卷:149

Article

Vallof, Daniel¹  Vestlund, Jesper¹  Jerlhag, Elisabet¹ 

[1] Univ Gothenburg, Sahlgrenska Acad, Dept Pharmacol, Inst Neurosci & Physiol, Med Regatan 13A, SE-40530 Gothenburg, Sweden

关键词: Alcohol use disorder;    Dopamine;    Reward;    Gut-brain axis;   

DOI  :  10.1016/j.neuropharm.2019.02.020

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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