Sleep is considered critical for maintaining physical and mental health.
Sleep deprivation is a type of stress that affects the human population globally. Stress increases plasma levels of
neurosteroids in the brain, which have potent effects on the GABAergic system. In the present study, we investigated the possible involvement of GABAergic modulation in the protective effect of
allopregnanolone on
sleep deprivation-induced anxiety-like behavior and oxidative damage in mice. Pretreatment with
allopregnanolone (10 and 20 mg/kg i.p.) significantly improved locomotor activity,
weight loss and anxiety-like behavior. Biochemically,
allopregnanolone treatment significantly restored
reduced glutathione and
catalase activity and attenuated elevated lipid peroxidation and
nitrite levels when compared with untreated 72-h sleep-deprived animals (P < 0.05). A combination of
flumazenil (0.5 mg/kg) and
picrotoxin (0.5 mg/kg) with
allopregnanolone (10 mg/kg) antagonized the protective effect of
allopregnanolone and caused further impairment in locomotor activity, anxiety-like behavior,
weight loss and oxidative damage. However,
muscimol (0.05 mg/kg) in combination with
allopregnanolone (10 mg/kg) potentiated its behavioral and
antioxidant effects. These effects were significant when compared with the effects of either agent alone (P < 0.05). The present study indicates that
allopregnanolone induces its protective effect by GABAergic modulation at various recognition sites on the
GABA-benzodiazepine receptor complex. It also suggests that
allopregnanolone could be used in the management of
sleep deprivation-induced anxiety-like behavior and related oxidative damage.