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Objective The current study was aimed to investigate the correlations between immobility time in the forced swimming test (FST, a behavioral indicator of stress level) and hippocampal monoamine levels (markers of depression), plasma adrenalin level (a peripheral marker of stress) as well as fl uoro-jade C staining (a marker of neurodegeneration).Methods Male Sprague-Dawley rats were subjected to acute, sub-chronic (7 d) or chronic (14 d) FSTs and immobility time was recorded. Levels of noradrenalin, serotonin and dopamine in the hippocampus, and adrenalin level in the plasma were quantified by high-performance liquid chromatography with electrochemical detection. Brain sections from rats after chronic forced swimming or rotenone treatment (3 mg/kg subcutaneously for 4 d) were stained with fl uoro-jade C. ResultsThe rats subjected to swimming stress (acute, sub-chronic and chronic) showed long immobility times [(214 ± 5), (220 ± 4) and (231 ± 7) s, respectively], indicating that the animals were under stress. However, the rats did not exhibit significant declines in hippocampal monoamine levels, and the plasma adrenalin level was not significantly increased compared to that in unstressed rats. The rats that underwent chronic swimming stress did not manifest fl uoro-jade C staining in brain sections, while degenerating neurons were evident after rotenone treatment. Conclusion The immobility time in the FST does not correlate with markers of depression (monoamine levels) and internal stress (adrenalin levels and neurodegeneration), hence this parameter may not be a true indicator of stress level.