Sleep is an important physiological process responsible for the maintenance of physical, mental and emotional health of a living being.
Sleep deprivation is considered risky for several pathological diseases such as anxiety and motor and
cognitive dysfunctions.
Sleep deprivation has recently been reported to cause oxidative damage. This study has been designed to explore the possible involvement of the GABAergic mechanism in protective effects of
melatonin against 72-h
sleep deprivation-induced behaviour modification and oxidative damage in mice. Mice were sleep-deprived for a period of 72 h using the grid over water suspended method. Animals were divided into groups of 6-8 animals each.
Melatonin (5 and 10 mg/kg),
flumazenil (0.5 mg/kg),
picrotoxin (0.5 mg/kg) and
muscimol (0.05 mg/kg) were administered for 5 days starting 2 days before 72-h
sleep deprivation. Various behavioural tests (plus maze, zero maze, mirror chamber, actophotometer) and
body weight assessment followed by oxidative stress parameters (
malondialdehyde level,
glutathione,
catalase,
nitrite and
protein) were carried out. The 72-h
sleep deprivation caused significant anxiety-like behaviour,
weight loss, impaired locomotor activity and oxidative damage as compared with naïve (without
sleep deprivation). Treatment with
melatonin (5 mg/kg and 10 mg/kg, ip) significantly improved locomotor activity,
weight loss and
antianxiety effect as compared with control (sleep-deprived). Biochemically,
melatonin treatment significantly restored
reduced glutathione,
catalase activity, attenuated lipid peroxidation and
nitrite level as compared with control animals (72-h sleep-deprived).
Flumazenil (0.5 mg/kg) and
picrotoxin (0.5 mg/kg) pretreatments with a lower dose of
melatonin (5 mg/kg) significantly antagonized the protective effect of
melatonin. However,
muscimol (0.05 mg/kg) pretreatment with
melatonin (5 mg/kg, ip) potentiated the protective effect of
melatonin which was significant as compared with their effect per se. This study suggests that GABAergic modulation is involved in the protective action of
melatonin against
sleep deprivation-induced anxiety-like behaviour and associated oxidative damage.