CHRONIC ANTIOXIDANT TREATMENT IMPROVES THE COGNITIVE PERFORMANCE OF AGED RATS

Free radicals and oxidative damage have been implicated in brain aging and several neurodegenerative diseases. The purpose of the present st udy was to determine whether antioxidants could alleviate age-associat ed cognitive and motor changes. Aged 24-month-old male Sprague-Dawley rats were treated for 4-5 months with daily i.p. injections of the spi n-trapping compound phenyl-alpha-tert-butylnitrone (PBN; 32 mg/kg) and alpha-tocopherol (200 mg/kg) or with vehicles. Antioxidant-treated an imals also received ascorbate in their drinking water. In Morris water maze testing after two months, antioxidant-treated rats had a greater rate of acquisition (learning), although overall acquisition was not affected. Moreover, antioxidant-treated rats exhibited significantly g reater memory retention than vehicle-treated rats in water maze testin g. Subsequent tests for passive avoidance behavior and motor activity/ skill revealed no effect of antioxidant treatment. In a separate group of aged 33-month-old rats that received the same combination of antio xidants for only 14 days, antioxidant treatment did not affect basal l evels of brain lipid peroxidation (as indexed by TEAR formation) compa red to controls. The results of this study provide initial evidence th at chronic antioxidant treatment can improve cognitive function during aging, thus supporting the 'free radical hypothesis of aging' related to brain function.