Background: Sleep loss is one of the most important health problems in the world, and about 30 to 40 percent of ordinary people suffer from it. This study aimed to investigate the neuroprotective effects of the combination of resveratrol and naringenin in attenuation of sleep deprivation (SD) complications in rats. Materials and Methods: In this experimental study, 72 Wistar male rats were randomly divided into three main groups, including control, sham, and 7-days SD group. Each of its main groups consisted of three subgroups, including without drug, vehicle, and combination therapy groups (naringenin [100 mg/kg], resveratrol [100 mg/kg]). The day after the latest injection, the fear conditioning memory tests, locomotor activity test, hot plate, and forced swimming tests (FST) were carried out on all rats, and then sham and SD groups were induced 48 hours of non-REM SD (device off and on, respectively) and these behavioral tests were repeated for all rats again. Finally, the brains of all rats were removed and histopathologically examined, and stained with nissl and TUNNEL. Results: To assess fear condition memory, the rate of latency to first freezing in the visual and auditory phase increased in sham and SD rats that received vehicle or no drug (P<0.001), which indicates memory corruption. Injection of the combination of naringenin and resveratrol reduced the latency to first freezing (P<0.001), which means improved memory. In the FST test, injection of naringenin and resveratrol reduced the rate of immobility (P<0.001), which means improved depressive behavior. The naringenin and resveratrol reduced the pain perception threshold. Also, the naringenin and resveratrol reduced apoptosis compared to the control and vehicle groups (P<0.001). Conclusions: The combination of naringenin and resveratrol compared to other groups could improve memory and mood as well as reduce apoptosis, depression, and pain perception threshold. [GMJ.2021;10:e2315]
Drug Vehicle Unit of Volume