Neuroprotective effect of carvedilol, an adrenergic antagonist against colchicine induced cognitive impairment and oxidative damage in rat

Abstract

Cognitive impairment and weak intellectual capacity is a gradually progressive neurodegenerative problem. Growing evidences indicate that oxidants and antioxidant defenses interact in a vicious cycle, which plays a critical role in the pathogenesis of cognitive dysfunction. The present study was carried out to elucidate the neuroprotective effect of carvedilol against the colchicine-induced cognitive impairment and oxidative damage in rats. Colchicine (15 µg/5 µl), a microtubule disrupting agent when administered intracerebroventricularly in rats resulted in poor memory retention in both Morris water maze, elevated plus maze task paradigms and caused marked oxidative stress as indicated by significant increase in malondialdehyde, nitrite levels, depletion of SOD, catalase, glutathione-S-transferase activity and reduced glutathione levels. It also caused a significant decrease in the acetylcholinesterase activity. Chronic administration of carvedilol (2.5 and 5.0 mg/kg; p.o.) for a period of 25 days, starting 4 days prior to colchicine administration resulted in an improvement in memory retention, attenuation of oxidative damage and restoration of acetylcholinesterase activity. Present study demonstrates a neuroprotective effect of carvedilol against colchicine-induced cognitive impairment and associated oxidative damage.