[Show abstract][Hide abstract] ABSTRACT: RationaleOur previous studies in rats have shown that the adipocyte-derived hormone leptin induces antidepressant-like effects with
a behavioral profile similar to selective serotonin reuptake inhibitor (SSRI) antidepressants. Acute SSRI treatment causes
paradoxical anxiogenic responses, although chronic treatment has therapeutic effects on anxiety. However, the role of leptin
in anxiety remains to be established.
ObjectivesThe scope of this study was to investigate the acute effects of leptin on anxiety-related behaviors in comparison with the
SSRI antidepressant fluoxetine.
Materials and methodsAdult male C57BL/6J mice received intraperitoneal injection of leptin or fluoxetine. Thirty minutes after injection, mice
were subjected to the tail suspension test (TST) and forced swim test (FST) for evaluating antidepressant activity. Anxiety-like
behavior was assessed in the elevated plus maze (EPM), social interaction, and open field tests 30min following drug treatment.
ResultsWhile leptin and fluoxetine showed similar antidepressant-like behavioral effects in the TST and FST, they differed in the
behavioral assays for anxiety. Open arm exploration in the EPM was increased by leptin but decreased by fluoxetine. Analysis
of social interaction revealed that distinct social behavioral components were modulated by leptin and fluoxetine. The total
time of active social behaviors was increased by leptin but reduced by fluoxetine. In addition, self-grooming, a non-social
behavior, was suppressed by leptin treatment. Neither leptin nor fluoxetine produced significant effects in the open field
ConclusionsIn contrast to anxiogenic-like effects induced by acute fluoxetine, leptin elicits anxiolytic-like effects after acute administration.
These results suggest that leptin has both antidepressant-like and anxiolytic-like properties.