Possible antioxidant mechanism in melatonin reversal of aging and chronic ethanol-induced amnesia in plus-maze and passive avoidance memory tasks

Cognitive dysfunction is one of the most striking age-related impairments s een in human beings and animals. This impairment probably is due to the vul nerability of the brain cells to increased oxidative stress during aging pr ocess. Pineal hormone melatonin is reported to be an endogenous antioxidant , whose peak plasma level declines during aging and in Alzheimer's disease (AD). Present experiments were performed to study the possible effect of ex ogenously administered melatonin on cognitive performance of young, aged, o r ethanol-intoxicated mice (an animal model for AD) using one trial step-do wn type of passive avoidance and elevated plus-maze task. Aged or chronic e thanol-treated mice showed poor retention of memory in step-down passive av oidance and in elevated plus-maze task. Chronic administration of melatonin (0.1-10 mg/kg, sc) for 30 d or its coadministration with ethanol (15% W/V, 2 g/kg perorally) for 24 d significantly reversed the age-induced or chron ic ethanol-induced retention deficits in both the test paradigms. However, in both the memory paradigms chronic administration of melatonin failed to modulate the retention performance of young mice. Chronic administration of melatonin (0.1-10 mg/kg) for 30 d also reversed age-associated decline in forebrain total glutathione (tGSH) level. Chronic ethanol administration to young mice produced decline in forebrain tGSH level and enhanced brain lip id peroxidation, which was significantly reversed by coadministration of me latonin (10 mg/kg). The results of this study showed chronic melatonin trea tment reverses cognitive deficits in aged and ethanol-intoxicated mice, whi ch is associated with its antioxidant property. (C) 2001 Elsevier Science I nc.