Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment

Recent reports suggest the involvement of free radicals in the pathophysiol ogy of Alzheimer's disease [AD]. Streptozotocin [STZ] injection in the brai n is known to cause cognitive impairment in rats and is likened to sporadic AD in humans. Though STZ is known to cause impairment in glucose and energ y metabolism, it is nut known whether this is associated with free radical generation. The present study was designed to investigate if the changes in learning and memory by intracerebroventricular administration of STZ are a ssociated with changes in the markers of oxidative stress. Adult male Wistar rats [330-340g] were injected with intracerebroventricula r STZ [3mg/kg] bilaterally stereotaxically under ketamine anesthesia [70mg/ kg]. The rats were treated with STZ twice, on day 1 and on day 3. The learn ing and memory behavior was analyzed using passive avoidance paradigms,elev ated plus maze and the closed field activity test while the parameters of o xidative stress assessed were malondialdehyde [MDA] and glutathione. The be havioral tests were performed on day 17, 18 and 19. The rats developed sign ificant deficits in learning, memory and cognitive behavior, indicated by d eficits in passive avoidance paradigm and elevated pins maze as compared to sham rats. On day 21, the rats were sacrificed under ether anesthesia and the brains were analyzed for biochemical studies. There was a development o f oxidative stress in the brain as indicated by significant elevations in m alondialdehyde [MDA] levels and decreased levels of glutathione. The study demonstrates that intracerebroventricular STZ may be appropriate model for investigations of antioxidants as potential treatment in Alzheimer's dement ia. (C) 2001 Elsevier Science Inc. All rights reserved.