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The effect of repeated Morris water maze tests on the ability of place navigation was examined in rats with permanent unilateral occlusion of the middle cerebral artery (MCA) and/or the ipsilateral common carotid artery (CCA), in relation to choline acetyltransferase (ChAT) immunoreactivity in the basal magnocellular nucleus of Meynert (NBM). The Morris water maze task was conducted 2, 4, 6 and 8 weeks after MCA or MCA/CCA occlusion; each test included two trials per day for 4 days, and the mean latency for the rats to reach an invisible platform below the water surface was measured. MCAor MCA/CCA-occluded rats subjected to repeated water maze tests exhibited only transient disability of place-navigation; the mean latency of MCAor MCA/CCA-occluded rats became close to that of sham-operated rats by 6 to 8 weeks after ischernia. Despite the time-dependent recovery of place-navigation activity in MCAor MCA/CCA-occluded rats, ChAT neurons in the NBM, which are considered to be involved primarily in spatial learning ability, were fewer on the ischemic side than on the non-ischemic side throughout the examination period. Moreover, hemispheric atrophic changes were prominent at later stages after MCA or MCA/CCA occlusion. These findings suggest that early water maze training facilitates the functional restoration of MCAor MCA/CCA-occluded rats, and that the recovery of place-navigation activity in the ischemic rats cannot necessarily be explained by a reduction in the ischemic injury of ChAT neurons in the NBM. ischemic lesions in the striatal or corticostriatal Cerebral infarction induces a variety of signs and symptoms including hemiplegia, reduced locomotion and cognitive disturbances. For studies of the mechanism(s) underlying ischemic neuronal death and in a search for new methods or drugs for the treatment of brain ischemia, several animal models have been developed. Rats with permanent middle cerebral artery (MCA) occlusion appear to be useful since they invariably develop infarcts in the striatum and/or cerebral cortex and mimic, at least in part, human patients with cerebral infarction (17), although the extent of the ischemic lesion varies with the strain, arterial pressure, blood glucose concentration and age of the rats (5). Since region of rats with MCA occulsion frequently include the cholinergic pathway from the basal magnocellular nucleus of Meynert (NBM) to the frontoparietal cortex (7), disruption of the acetylcholine neuron system which is primarily involved in space learning activity (ll) may lead to a cognitive deficitin MCA-occluded rats. Rats with transient MCA occlusion, when examined once with the Morris water maze (12) 2 or 3 months after ischemia, have been reported to exhibit space-navigation impairment (l). However, it remains to be determined whether or not impairment of spatial learning in rats with MCA occlu-

<b>SPATIAL LEARNING DISABILITY IN RATS WITH FOCAL CEREBRAL ISCHEMIA RECOVERS BY REPEATING MORRIS WATER MAZE </b><b>TESTS </b>