期刊
NEUROPSYCHOPHARMACOLOGY
卷 42, 期 10, 页码 2052-2063出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2017.60
关键词
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资金
- Hope for Depression Research Foundation
- NIH [MH068542, DA022413, MH106731, MH112861]
- New Jersey Health Foundation
- New Jersey Governor's Council on Autism
- Columbia University College of Physicians Surgeons
- NARSAD
Depression is a debilitating chronic illness that affects around 350 million people worldwide. Current treatments, such as selective serotonin reuptake inhibitors, are not ideal because only a fraction of patients achieve remission. Tianeptine is an effective antidepressant with a previously unknown mechanism of action. We recently reported that tianeptine is a full agonist at the mu opioid receptor (MOR). Here we demonstrate that the acute and chronic antidepressant-like behavioral effects of tianeptine in mice require MOR. Interestingly, while tianeptine also produces many opiate-like behavioral effects such as analgesia and reward, it does not lead to tolerance or withdrawal. Furthermore, the primary metabolite of tianeptine (MC5), which has a longer half-life, mimics the behavioral effects of tianeptine in a MOR-dependent fashion. These results point to the possibility that MOR and its downstream signaling cascades may be novel targets for antidepressant drug development.
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