Recently, the metabolic aspects of depression have been the focus of many studies. Several metabolic disorders, such as obesity and diabetes, are the main risk factors for depression The successful application of antidiabetic agents in treating neurological diseases suggests that similar drugs may also have beneficial effects on depression. New research in animals has shown that the diabetes drug dulaglutide, which is a glucagon-like peptide-1 (GLP-1) receptor agonist, may reduce symptoms of depression. The findings provide a new perspective for understanding the antidepressant-like effects of dulaglutide and may lead the use of dulaglutide as a potential therapeutic strategy for depression.

The new study was published in the journal Brain and Behavior in an article titled, “Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress,” and led by researchers at the Hebei Medical University and Hebei General Hospital.

Dulaglutide is a medication used for the treatment of type 2 diabetes in combination with diet and exercise. It is approved in the United States for the reduction of major adverse cardiovascular events in adults with type 2 diabetes who established cardiovascular disease or multiple cardiovascular risk factors.

“Treatment strategies for depression based on interventions for glucose and lipid metabolism disorders are receiving increasing attention, noted the researchers. “Investigating the mechanism of their antidepressant effect and exploring new diagnostic and therapeutic biomarkers have attracted increasing attention. Dulaglutide, a long-acting GLP-1 receptor agonist, has been reported to alleviate cognitive deficits and neuronal damage. However, the antidepressant effect of dulaglutide and, especially, the underlying mechanism are still poorly understood. In this study, we aimed to explore the underlying biomarkers of depression and potential modulatory targets of dulaglutide in chronic mild stress (CMS) mice.”

By conducting a range of tests in mice treated with and without dulaglutide, the researchers observed three weeks of dulaglutide treatment significantly reversed depressive-like but not anxiety-like behaviors in mice exposed to chronic stress for four weeks.

The researchers confirmed the effects of dulaglutide in a CMS depression model. They identified 64 different metabolites and four major pathways in the brain associated with these effects.

Markers of depression and the antidepressant effects of dulaglutide were linked to lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism.

“These primary data provide a new perspective for understanding the antidepressant-like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression,” the authors wrote.

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