Kamat PK, Tota S, Saxena G, Shukla R, Nath C
Okadaic acid (ICV) induced memory impairment in rats: A suitable experimental model to test anti-dementia activity. [JOURNAL ARTICLE]
Brain Res 2009 Oct 30.
Okadaic acid (OKA) is a potent and selective inhibitor of protein phosphatases, PP2A and PP1. In the present study, we evaluated effect of Intracerebroventricular (ICV) bilateral injection of OKA (100 and 200ng) on memory function and oxidative stress in rats. ICV injection of OKA (200ng) produced memory impairment as evidenced by no significant decrease in latency time to reach the hidden platform in water maze test. It produced increase in malondialdehyde (MDA), nitrite level, reactive oxygen species (ROS) generation, mitochondrial calcium ion [Ca(2+)]i level and decreased glutathione (GSH) level in rat brain areas, indicating oxidative stress. Further, we evaluated the effect of antidementia drugs memantine, a NMDA antagonist, and donepezil, a cholinesterase inhibitor, on OKA ICV induced memory impairment. Administration of Memantine (10mg/kg, p.o.) and donepezil (5 mg/kg, p.o.) for 13 days starting from the OKA injection improved performance in memory tests and also significantly restored GSH, MDA, nitrite levels , ROS generation and [Ca(2+)]i level. This study demonstrates that the clinically used antidementic drugs are effective in OKA induced free radical generation and memory impairment in rats. Thus, OKA ICV induced memory impairment in rat appeared as a useful test model to screen antidementia drugs.
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