Spatial discrimination deficits by excitotoxic lesions in the Morris water escape task.
The effects of the cholinesterase inhibitors (ChEI) metrifonate and donepezil were assessed on spatial performance of rats with bilateral lesions of the entorhinal cortex (EC), which is thought to model early changes in the brains of patients suffering from Alzheimer's disease. In the present study, we found that spatial discrimination deficits in rats, induced by bilateral ibotenic acid (IBO) lesions of the EC region can partially be antagonised by treatment with the cholinesterase inhibitors metrifonate (30 mg kg(-1)) and donepezil (0.3 and 3 mg kg(-1)). Performance was improved in the spatial discrimination task compared with that of the EC-lesioned control group. It is concluded that the rat with bilateral EC lesions is a suitable deficit model for the assessment of effects of putative Alzheimer therapeutics.
Spowart-Manning
L
L
Department of Pharmacology and Therapeutics, Trinity College Dublin, Dublin 2, Ireland. spowart1@tcd.ie
van der Staay
F J
FJ
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018728:Entorhinal Cortex / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology*; D004924:Escape Reaction / Q000187:drug effects* / Q000502:physiology; D007051:Ibotenic Acid / Q000633:toxicity; D008297:Male; D018782:Maze Learning; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000187:drug effects* / Q000502:physiology; D014236:Trichlorfon / Q000008:administration & dosage*
D002800:Cholinesterase Inhibitors; D007051:Ibotenic Acid; D014236:Trichlorfon