BDNF signaling is necessary for the antidepressant-like effect of naringenin

- Naringenin reverses sucrose preference and first feeding latency in CUMS.
- Naringenin up-regulates BDNF levels in hippocampus but not in frontal cortex.
- K252a blocks the antidepressant-like effect of naringenin.

Previous studies in our laboratory have demonstrated that naringenin produced antidepressant-like action in tail suspension test (TST). However, the underlying mechanisms involved in neurotrophin system by which naringenin works have not been investigated. The present study extends earlier works on the role of brain-derived neurotrophic factor (BDNF) in regulating the antidepressant-like actions of naringenin in chronic unpredictable mild stress (CUMS). We showed that a 21-day regimen with naringenin reversed the decreased sucrose preference in sucrose preference test (SPT) and the prolonged first feeding latency in novelty-suppressed feeding test (NSFT), without affecting home-cage feeding consumption. In addition, we also found that naringenin promoted BDNF expression in the hippocampus but not in the frontal cortex in both non-stressed and CUMS mice. Moreover, the antidepressant-like effect of naringenin in SPT and NSFT induced by naringenin administration were totally abolished by K252a, an inhibitor of BDNF receptor tropomyosin-related kinase receptor B (TrkB). In conclusion, our findings suggest that the antidepressant-like effect of naringenin may be mediated, at least in part, by the activation of BDNF signaling in the hippocampus.