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Okadaic acid (ICV) induced memory impairment in rats: a suitable experimental model to test anti-dementia activity.
Brain Res. 2010 Jan 14; 1309:66-74.BR

Abstract

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 [Ca(2)](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 [Ca(2+)](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.

Authors+Show Affiliations

Division of Pharmacology, Central Drug Research Institute, Lucknow (U.P.), India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19883632

Citation

Kamat, Pradeep K., et al. "Okadaic Acid (ICV) Induced Memory Impairment in Rats: a Suitable Experimental Model to Test Anti-dementia Activity." Brain Research, vol. 1309, 2010, pp. 66-74.
Kamat PK, Tota S, Saxena G, et al. Okadaic acid (ICV) induced memory impairment in rats: a suitable experimental model to test anti-dementia activity. Brain Res. 2010;1309:66-74.
Kamat, P. K., Tota, S., Saxena, G., Shukla, R., & Nath, C. (2010). Okadaic acid (ICV) induced memory impairment in rats: a suitable experimental model to test anti-dementia activity. Brain Research, 1309, 66-74. https://doi.org/10.1016/j.brainres.2009.10.064
Kamat PK, et al. Okadaic Acid (ICV) Induced Memory Impairment in Rats: a Suitable Experimental Model to Test Anti-dementia Activity. Brain Res. 2010 Jan 14;1309:66-74. PubMed PMID: 19883632.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Okadaic acid (ICV) induced memory impairment in rats: 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, Y1 - 2009/10/31/ PY - 2009/07/24/received PY - 2009/09/22/revised PY - 2009/10/25/accepted PY - 2009/11/4/entrez PY - 2009/11/4/pubmed PY - 2010/2/27/medline SP - 66 EP - 74 JF - Brain research JO - Brain Res VL - 1309 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 [Ca(2)](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 [Ca(2+)](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. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/19883632/Okadaic_acid__ICV__induced_memory_impairment_in_rats:_a_suitable_experimental_model_to_test_anti_dementia_activity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(09)02301-4 DB - PRIME DP - Unbound Medicine ER -