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- W2206575616 abstract "Glucagon-like peptide 1 (GLP-1), produced in the intestine and hindbrain, is known for its glucoregulatory and appetite suppressing effects. GLP-1 agonists are in clinical use for treatment of type 2 diabetes and obesity. GLP-1, however, may also affect brain areas associated with emotionality regulation. Here we aimed to characterize acute and chronic impact of GLP-1 on anxiety and depression-like behavior. Rats were subjected to anxiety and depression behavior tests following acute or chronic intracerebroventricular or intra-dorsal raphe (DR) application of GLP-1 receptor agonists. Serotonin or serotonin-related genes were also measured in the amygdala, DR and the hippocampus. We demonstrate that both GLP-1 and its long lasting analog, Exendin-4, induce anxiety-like behavior in three rodent tests of this behavior: black and white box, elevated plus maze and open field test when acutely administered intraperitoneally, into the lateral ventricle, or directly into the DR. Acute central GLP-1 receptor stimulation also altered serotonin signaling in the amygdala. In contrast, chronic central administration of Exendin-4 did not alter anxiety-like behavior but significantly reduced depression-like behavior in the forced swim test. Importantly, this positive effect of Exendin-4 was not due to significant body weight loss and reduced food intake, since rats pair-fed to Exendin-4 rats did not show altered mood. Collectively we show a striking impact of central GLP-1 on emotionality and the amygdala serotonin signaling that is divergent under acute versus chronic GLP-1 activation conditions. We also find a novel role for the DR GLP-1 receptors in regulation of behavior. These results may have direct relevance to the clinic, and indicate that Exendin-4 may be especially useful for obese patients manifesting with comorbid depression." @default.
- W2206575616 created "2016-06-24" @default.
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- W2206575616 creator A5085002016 @default.
- W2206575616 date "2016-03-01" @default.
- W2206575616 modified "2023-10-10" @default.
- W2206575616 title "GLP-1 is both anxiogenic and antidepressant; divergent effects of acute and chronic GLP-1 on emotionality" @default.
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- W2206575616 doi "https://doi.org/10.1016/j.psyneuen.2015.11.021" @default.
- W2206575616 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26724568" @default.
- W2206575616 hasPublicationYear "2016" @default.
- W2206575616 type Work @default.