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Neuropsychopharmacology. 2017 Sep;42(10):2052-2063. doi: 10.1038/npp.2017.60. Epub 2017 Mar 17.

The Behavioral Effects of the Antidepressant Tianeptine Require the Mu-Opioid Receptor.

Author information

1
Department of Psychology, Behavioral &Systems Neuroscience, Rutgers, The State University of New Jersey-New Brunswick, Piscataway, NJ, USA.
2
Department of Psychiatry, Columbia University, and Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, NY, USA.
3
Department of Chemistry and NeuroTechnology Center, Columbia University, New York, NY, USA.
4
Department of Biology, Columbia University, New York, NY, USA.
5
Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA.

Abstract

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.

PMID:
28303899
PMCID:
PMC5561344
DOI:
10.1038/npp.2017.60
[Indexed for MEDLINE]
Free PMC Article

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