Modelling cognitive dysfunctions with bilateral injections of ibotenic acid into the rat entorhinal cortex

Neurodegenerative diseases, traumatic brain injury and stroke are likely to result in cognitive dysfunctioning. Animal models are needed in which thes e deficits and recovery of the affected functions can be investigated. In t he present study, the entorhinal area was chosen as the target for lesionin g and for assessing the lesion-induced deficits in the Morris water maze. T he entorhinal cortex is regarded as an interface between the hippocampus an d neocortex. Deafferentiating the hippocampus through entorhinal lesions im pairs spatial learning. The effects of lesions, induced by either electroco agulation (experiment 1) or ibotenate excitotoxicity (experiment 2), on spa tial orientation behaviour were investigated. Water maze performance after unilateral or bilateral ibotenate injections into the entorhinal cortex was studied in the third experiment. In an additional study, the replicability of the spatial learning deficit after lesions induced by bilateral injecti ons of ibotenic acid into the entorhinal cortex was assessed by comparing t he results of nine experiments. We found that spatial learning was impaired after bilateral lesions aimed at the entorhinal cortex. The electrolytic l esion technique produced a relatively large sham effect, whereas the excito toxic lesioning method did not. Unilateral injections of ibotenic acid into the entorhinal cortex did not affect spatial navigation. The ibotenate ind uced lesions replicably produced deficits in the Morris tasks. The degree o f the induced spatial learning impairments and the effects on the rate of a cquisition during training, however, differed between experiments. This res ult suggests that the fundamental biological diversity between shipments of rats can account for variation in the effects of parahippocampal damage on spatial learning even in highly standardized experimental set-ups. Rats lesioned by bilateral injections of ibotenic acid into the entorhinal cortex provide an interesting and reliable model for investigating cognitiv e dysfunctions in neurodegenerative diseases, stroke or traumatic brain inj ury. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.