Intracerebroventricular administration of colchicine produces cognitive impairment associated with oxidative stress in rats

Oxidative stress has been implicated in neurodegenerative disorders including the Alzheimer's disease (AD). Central administration of colchicine is known to cause cognitive impairment in rats and is likened to sporadic AD in humans. However, it is not known whether this cognitive impairment is associated with free radical generation. Therefore, in the present study, the effect of intracerebroventricular colchicine was studied on paradigms of learning and memory behavior and the markers of oxidative stress in rats. Adult male Wistar rats (200-250 g) were injected with colchicine (intracerebroventricular) bilaterally (15 mug/rat; 7.5 mug/site) on the first day. The learning and memory behavior was assessed using passive avoidance paradigm, elevated plus maze and closed field activity test on Days 13, 14 and 21. The parameters of oxidative stress were assessed by measuring the malondialdehyde (MDA), glutathione, superoxide dismutase (SOD) and catalase levels in brain tissue on Day 21 of the colchicine injection. The rats developed significant learning and memory impairment as indicated by deficit in behavioral paradigms. There was a significant elevation in MDA levels and decrease in levels of glutathione. No significant difference was observed in SOD and catalase levels. Thus, the study demonstrates that central administration of colchicine causes impairment in learning and memory with associated increase in oxidative stress. (C) 2002 Elsevier Science Inc. All rights reserved.