Antidepressant-Like Effect of Fluoxetine May Depend on Translocator Protein Activity and Pretest Session Duration in Forced Swimming Test in Mice

The study, involving 94 ICR (CD-1) male mice, explored the antidepressant-like effects of fluoxetine in the forced swimming test (FST) and the influence of the mitochondrial translocator protein (TSPO) and pretest session duration. It was found that fluoxetine at a dose of 20 mg/kg administered intraperitoneally was effective only when mice underwent a 5-minute pretest session 24 hours before the FST. The TSPO antagonist PK11195 was shown to inhibit fluoxetine's antidepressant effect. Additionally, the study suggested that a pretest duration of 5-10 minutes is optimal for demonstrating fluoxetine's antidepressant effects, while a 20-minute pretest may be excessively stressful and interfere with the drug's efficacy, potentially due to alterations in GABA_A-receptor function or neuroactive steroid system dysregulation. The findings highlight the importance of TSPO activity and appropriate pretest session duration in assessing the antidepressant activity of fluoxetine and similar drugs. The research was funded by the Russian Foundation for Basic Research and reported no conflicts of interest.