Gap junction is essential for the antidepressant effects of fluoxetine.

The article investigates the role of gap junction dysfunction in the delayed antidepressant effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI) used as first-line therapy for major depressive disorder (MDD). Using animal models subjected to chronic unpredictable stress (CUS), the study found that fluoxetine improved gap junction intracellular communication (GJIC) and alleviated depressive-like behaviors after six days, paralleling the typical time lag in therapeutic efficacy. Furthermore, blocking gap junctions in the prefrontal cortex with carbenoxolone (CBX) inhibited fluoxetine’s antidepressant effects in mice, suggesting that functional gap junctions are necessary for fluoxetine’s behavioral benefits. These findings highlight gap junction dysfunction as a potential mechanism underlying the delayed onset of fluoxetine’s antidepressant action.