Spatial learning deficits in rats after injection of vincristine into the dorsal hippocampus

In the present study, performance in the Morris water escape task after bil ateral lesioning of the dorsal hippocampus induced by the microtubule poiso n vincristine is discussed as a cognitive deficit model in rats. As we are especially interested in spontaneous or pharmacologically induced recovery processes after experimentally induced cognitive dysfunctions, the model sh ould fulfil a number of criteria. Firstly, a clear dose-effect relationship between the dose of vincristine and the amount of spatial learning impairm ents should be present. Secondly, lesions must remain within the target are a. Thirdly, there should be an observable behavioural recovery or compensat ion of the induced deficit. Two experiments evaluated the influence of the application volume (experiment 1) and the concentration of vincristine (exp eriment 2) on lesion location and size, and on spatial learning. The results of both experiments demonstrated that the effect of vincristine on the performance in the Morris water escape task seems to be characteriz ed by an "all-or-none" relationship. Concentrations above a "threshold" val ue induced severe damage in the hippocampus and adjacent brain structures, whereas concentrations below the "threshold" value had marginal or no effec ts. The non selective and highly toxic properties of vincristine make this neurotoxin an unsuitable tool for the establishment of a learning and memor y deficit model. (C) 1999 IBRO. Published by Elsevier Science Ltd.