Resveratrol attenuates chronic social isolation stress‐induced affective disorders: Involvement of NF‐κB/NLRP3 axis

Abstract

AbstractSocial isolation stress (SIS) is associated with affective disorders (i.e., anxiety and depression) in adults. In a preclinical study, we aimed to investigate the effects of resveratrol (RV) on the mood swings of rats exposed to SIS. Animals were randomized into six different groups, including control: healthy animals received normal saline (NS) as a vehicle; SIS + NS: SIS animals received NS; SIS + FL: SIS animals received fluoxetine (10 mg/kg/i.p.); SIS + RV20, SIS + RV40, and SIS + RV80: SIS animals received RV (20, 40, and 80 mg/kg/i.p). SIS was induced for 4 weeks, then animals were treated with NS, FL, and RV for 4 weeks. Rats were evaluated by the behavioral tests, including the elevated plus‐maze, tail suspension test, the open field test, and forced‐swimming test, for mood alterations and nuclear factor kappa B (NF‐κB) levels, along with NLRP3, apoptosis‐associated speck‐like (ASC), and proCaspase‐1 were determined in the hippocampus. Behavioral tests confirmed that exposing the animals to SIS caused anxiety and depression. The highest concentrations of NLRP3, proCaspase‐1, ASC, and NF‐κB, were confirmed in the SIS + NS group. Compared to FL, RV showed antidepressant potential according to the behavioral tests. In particular, the administration of RV (20, 40, and 80 mg/kg) revered the NF‐κB/NLRP3 axis cascade in rats exposed to chronic SIS. Our findings revealed that RV attenuated anxiety and depression of SIS‐exposed rats via regulation of NF‐κB/NLRP3 signaling pathways. RV can be used as a potential anxiolytic agent and antidepressant.