Antidepressant-like effect of acute dose of Naringin involves suppression of NR1 and activation of protein kinase A/cyclic adenosine monophosphate response element-binding protein/brain-derived neurotrophic factor signaling in hippocampus

Naringin (Nr) has been identified to have antidepressant-like effects through repeated treatment. However, the underlying mechanism of the rapid antidepressant-like effects of Nr was still unclear. The present study used behavioral tests, classic depressive model and pharmacological methods to reveal the rapid antidepressant-like potential of Nr. We found that a single dose of Nr (20 mg/kg) produced antidepressant-like action after 2 h in the tail suspension test (TST) and forced swimming test (FST). Moreover, ketamine-like effects were also demonstrated by using the chronic mild stress model (CMS) and learned helplessness (LH), and the results showed that Nr reversed all behavioral defects, TST, FST, source preference test (SPT) in CMS, and LH testing, TST, FST in LH model, at 2 h after a single administration. In addition, Nr (20 mg/kg) could improve the abnormal expressions of NMDA receptor NR1 and PKA/CREB/BDNF pathway in hippocampus 2 h after a single administration in CMS mice. Further investigation revealed that activation of NMDA receptors by NMDA (750 mg/kg) could block the antidepressant effects of acute administration of Nr (20 mg/kg). However, the inhibition of NMDA receptors by MK-801 (0.05 mg/kg) promoted the subdose of Nr (10 mg/kg) to have antidepressant effect, which was similar to the effective dose Nr (20 mg/kg). Taken together, acute dose of Nr produces rapid antidepressant-like action, and the underlying mechanism could be through inhibiting NMDA receptors in the hippocampus.