Organic cation transporter 2 contributes to SSRI antidepressant efficacy by controlling tryptophan availability in the brain.

ABSTRACT: Selective serotonin reuptake inhibitors (SSRI) are common first-line treatments for major depression. However, a significant number of depressed patients do not respond adequately to these pharmacological treatments. In the present preclinical study, we demonstrate that organic cation transporter 2 (OCT2), an atypical monoamine transporter, contributes to the effects of SSRI by regulating the routing of the essential amino acid tryptophan to the brain. Contrarily to wild-type mice, OCT2-invalidated mice failed to respond to prolonged fluoxetine treatment in a chronic depression model induced by corticosterone exposure recapitulating core symptoms of depression, i.e., anhedonia, social withdrawal, anxiety, and memory impairment. After corticosterone and fluoxetine treatment, the levels of t

SUBMITTER: Orrico-Sanchez A 

PROVIDER: S-EPMC10542329 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature