Spatial memory deficit and neurodegeneration induced by the direct injection of okadaic acid into the hippocampus in rats.
We investigated the effects of okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, on spatial memory and neuronal survival in rats. Rats were initially trained on a spatial memory task in an eight arm radial maze. Spatial reference and working memory was impaired 1 day after the unilateral microinjection of OA into the dorsal hippocampus. The impairment was transient, and had disappeared by the following day. In contrast, neurodegeneration induced by OA was persistent and extended to the contralateral side 13 days after the injection. These results suggest that OA causes spatial memory impairment and neurodegeneration when injected directly into the hippocampus. Our findings also indicate dissociation between memory impairment and neurodegeneration induced by OA.
He
J
J
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yamada
K
K
Zou
L B
LB
Nabeshima
T
T
D000818:Animals; D002452:Cell Count; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D009498:Neurotoxins; D019319:Okadaic Acid; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases