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

Social 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.