Possible involvement of GABAergic mechanism in protective effect of melatonin against sleep deprivation-induced behavior modification and oxidative damage in mice

Sleep deprivation for 72 h caused anxiety like behavior, weight loss, impaired locomotor activity and oxidative damage as indicated by increase in lipid peroxidation, nitrite level and depletion of reduced glutathione and catalase activity in sleep deprived mice brain. Treatment with melatonin (5 and 10 mg/kg, ip) significantly improved locomotor activity, weight loss and antianxiety effect as compared to control (sleep deprived). Biochemically, melatonin treatment significantly restored depleted reduced glutathione, catalase activity, attenuated lipid peroxidation and nitrite level as compared to control (72 h sleep-deprived) animals. A combination of flumazenil (0.5 mg/kg, ip) and picrotoxin (0.5 mg/kg, ip) with lower dose of melatonin (5 mg/kg, ip) significantly antagonized the protective effect of melatonin. However, combination of muscimol (0.05 mg/kg, ip) with melatonin (5 mg/kg, ip) potentiated protective effect of melatonin as compared to their effect per se. The results suggest that melatonin may produce its protective effect by involving GABAergic system against sleep deprivation-induced anxiety like behavior and related oxidative damage.