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 seen in human beings and animals. This impairment probably is due to the vulnerability of the brain cells to increased oxidative stress during aging process. 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 exogenously administered melatonin on cognitive performance of young, aged, or ethanol-intoxicated mice (an animal model for AD) using one trial step-down type of passive avoidance and elevated plus-maze task. Aged or chronic ethanol-treated mice showed poor retention of memory in step-down passive avoidance 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 chronic 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 lipid peroxidation, which was significantly reversed by coadministration of melatonin (10 mg/kg). The results of this study showed chronic melatonin treatment reverses cognitive deficits in aged and ethanol-intoxicated mice, which is associated with its antioxidant property.
Raghavendra
V
V
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D000647:Amnesia / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003627:Data Interpretation, Statistical; D003704:Dementia / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D000431:Ethanol; D008315:Malondialdehyde; D005978:Glutathione; D008550:Melatonin