TY - JOUR
T1 - Okadaic acid (ICV) induced memory impairment in rats
T2 - A suitable experimental model to test anti-dementia activity
AU - Kamat, Pradeep K.
AU - Tota, Santoshkumar
AU - Saxena, Gunjan
AU - Shukla, Rakesh
AU - Nath, Chandishwar
N1 - Funding Information:
Financial support to Pradeep Kumar Kamat and Santoshkumar Tota from Council of Scientific and Industrial Research (CSIR) New Delhi, India, is gratefully acknowledged.
PY - 2010/1/14
Y1 - 2010/1/14
N2 - 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 200 ng) on memory function and oxidative stress in rats. ICV injection of OKA (200 ng) 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 [Ca2]i level and decreased glutathione (GSH) level in rat brain areas, indicating oxidative stress. Furthermore, we evaluated the effect of anti-dementia drugs memantine, a NMDA antagonist, and donepezil, a cholinesterase inhibitor, on OKA ICV induced memory impairment. Administration of memantine (10 mg/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 [Ca2+]i level. This study demonstrates that the clinically used anti-dementic 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 anti-dementia drugs.
AB - 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 200 ng) on memory function and oxidative stress in rats. ICV injection of OKA (200 ng) 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 [Ca2]i level and decreased glutathione (GSH) level in rat brain areas, indicating oxidative stress. Furthermore, we evaluated the effect of anti-dementia drugs memantine, a NMDA antagonist, and donepezil, a cholinesterase inhibitor, on OKA ICV induced memory impairment. Administration of memantine (10 mg/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 [Ca2+]i level. This study demonstrates that the clinically used anti-dementic 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 anti-dementia drugs.
KW - Donepezil
KW - Excitotoxicity
KW - Memantine
KW - Memory impairment
KW - Morris water maze
KW - Okadaic acid
KW - Oxidative stress
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U2 - 10.1016/j.brainres.2009.10.064
DO - 10.1016/j.brainres.2009.10.064
M3 - Article
C2 - 19883632
AN - SCOPUS:72049129673
SN - 0006-8993
VL - 1309
SP - 66
EP - 74
JO - Brain Research
JF - Brain Research
ER -