Effect of chronic treatment of melatonin on learning, memory and oxidativedeficiencies induced by intracerebroventricular streptozotocin in rats

Intracerebroventricular (ICV) streptozotocin (STZ) has been shown to cause cognitive impairment, which is associated with free radical generation in t he brain of rats. Melatonin is a potent free radical scavenger and antioxid ant. In the present study, the effect of melatonin was investigated against ICV STZ induced cognitive impairment and oxidative stress in rats. Adult m ale Wistar rats were injected with ICV STZ (3 mg/kg) bilaterally. The rats were treated with STZ twice, on days I and 3. The learning and memory behav ior was assessed using passive avoidance paradigms, elevated plus maze and the closed field activity while the parameters of oxidative stress assessed were malondialdehyde (MDA) and glutathione. The rats were treated chronica lly with melatonin for 21 days starting from day I of STZ injection. The le arning and memory behavior was evaluated on days 17, 18 and 19 and the rats were sacrificed on day 21 for estimation of MDA and glutathione. The rats treated with melatonin showed significantly less cognitive impairment. Ther e was also insignificant increase in brain MDA and decrease in glutathione levels in melatonin-treated ICV STZ rats as compared to the vehicle-treated ICV STZ animals. The study demonstrates the effectiveness of melatonin in preventing the cognitive deficits as well as the oxidative stress caused by ICV STZ in rats and suggests it's potential in age and age-related neurode generative disorders where oxidative stress and cognitive impairment are in volved. (C) 2001 Elsevier Science Inc. All rights reserved.