AI Article Synopsis
- Tianeptine is shown to activate mu-opioid receptors (MOR), which contributes to its effects on depression and anxiety.
- The study tested tianeptine's action in MOR+/+ and MOR-/- mice, revealing that its analgesic, locomotor, and rewarding effects depend on the presence of MOR.
- Chronic use of tianeptine may lead to tolerance, indicating a potential concern for long-term treatment.
Article Abstract
Introduction: Tianeptine is approved in some countries to treat depression and anxiety. In addition to its activity on serotonin and glutamate neurotransmission, tianeptine has been proven to be a mu-opioid receptor (MOR) agonist, but only a few preclinical studies have characterized the opioid-like behavioral effects of tianeptine.
Methods: In this study, we tested tianeptine activity on G protein activation using the [S35] GTPγS binding assay in brain tissue from MOR+/+ and MOR-/- mice. Then, to determine whether tianeptine behavioral responses are MOR-dependent, we characterized the analgesic, locomotor, and rewarding responses of tianeptine in MOR+/+ and MOR-/- mice using tail immersion, hot plate, locomotor, and conditioned place preference tests.
Results: Using the [S35] GTPγS binding assay, we found that tianeptine signaling is mediated by MOR in the brain with properties similar to those of DAMGO (a classic MOR agonist). Furthermore, we found that the MOR is necessary for tianeptine's analgesic (tail immersion and hot plate), locomotor, and rewarding (conditioned place preference) effects. Indeed, these behavioral effects could only be measured in MOR+/+ mice but not in MOR-/- mice. Additionally, chronic administration of tianeptine induced tolerance to its analgesic and hyperlocomotor effects.
Discussion: These findings suggest that tianeptine's opioid-like effects require MOR and that chronic use could lead to tolerance.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10242025 | PMC |
| http://dx.doi.org/10.3389/fpsyt.2023.1186397 | DOI Listing |
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