4.6 Article

Chronic tianeptine induces tolerance in analgesia and hyperlocomotion via mu-opioid receptor activation in mice

Journal

FRONTIERS IN PSYCHIATRY
Volume 14, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fpsyt.2023.1186397

Keywords

opioid; tail immersion; locomotor activity; place preference; mu-opioid receptor (MOR); tianeptine

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This study found that the antidepressant tianeptine mainly exerts its effects on the brain through the μ-opioid receptor, and it exhibits analgesic, locomotor, and rewarding behaviors in animal models. These effects can only be observed in mice with positive expression of the opioid receptor, and are ineffective in mice with negative expression. In addition, chronic use of tianeptine may lead to tolerance to its analgesic and hyperlocomotor effects.
IntroductionTianeptine 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. MethodsIn this study, we tested tianeptine activity on G protein activation using the [S35] GTP gamma S 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. ResultsUsing the [S35] GTP gamma S 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. DiscussionThese findings suggest that tianeptine's opioid-like effects require MOR and that chronic use could lead to tolerance.

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