Transient impairment of spatial learning after focal cerebral ischemia in rats subjected to repeated morris water maze tests

Transient impairment of spatial learning after focal cerebral ischemia in rats subjected to repeated morris water maze tests

2315 NAB- EFFECTS OF THE INHIBITION OF NITRIC OXIDE SYNTHASE ON LEARNING AND MEMORY IN RATS. &IYOFUMI YAMBDA. YIJKMIpO NODA. sm l&t. of 5 Sch. off N...

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2315 NAB-

EFFECTS OF THE INHIBITION OF NITRIC OXIDE SYNTHASE ON LEARNING AND MEMORY IN RATS. &IYOFUMI YAMBDA. YIJKMIpO NODA. sm l&t. of 5 Sch. off

Nitric oxide (NO), a putative intercellular messenger molecule, has been demonstrated to play a role in certain forms of learning and memory. We investigated the effects of No-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, on the performance in radial arm maze and habituation tasks in rats. The content of dopamine (DA), serotonin (MIT) and their metabolites in the discrete brain areas of LNAME-treated rats was also determined after these behavioral tests. The daily administration of L-NAME (10-60 mgJkg, i.p.) over the lo-day training period resulted in a dose-dependent impairment of the acquisition of the task, while No-nitroD-arginine methyl ester (D-NAME, 60 mg/kg, i.p.) had no effect. In contrast, LNAME (l-lOOmg/kg, i.p.) failed to impair the recall of memory when rats had previously acquired the maze task. The rate of decrease in motor activity on the 2nd day in habituation task in the L-NAME-treated rats was less than that in conaol and D-NAME-treatedrats. 5Hydroxyindoleacetic acid (5-HIAA) eontent in the hippoeampus and the ratio of 5-H&4/5-HT in the hippocampus and cortex significantly decreased in the L-NAME (6Omg/kg)-treated rats as compared with those in control and the D-NAME-treated rats, while the striatal 3,4dihydroxyphenylacetic acid content significantly increased in the L-NAME (fXkn@g)-treated rats. These results suggest that NO may play an important role in the acquisition but not maintenance of spatial learning in radial maze task. In addition, it is suggested that endogenous NO may be involved in the regulation of the metabolism of DA and 5-HT in the brain.

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AGE-RELATED IMPAIRMENT IN SPATIAL LEARNING Susumu ANDOi, Satoru KOBAYASHP, Yasushi OHASI-IV, Kotaro TANEICHIJ

iDepartment of Membrane Biochemistry, and 2Department of Experimental Biology, Tokyo Metropolitan Institute of Gerontology, Sakaecho, Itabashi, Tokyo 173; 3Public Health Research Foundation, Waseda, Shinzyuku 169; “Graduate School of Literature, Waseda University, Waseda, Shinzyuku 169. Learning ability of aged rats is much lower than that of young ones, as revealed by our previous study using maze tests according to Hebb-Williams. Behavioral characteristics, however, leading to errors have not been interpreted. In this study, we have employed a newly developed maze task called AKON-1, and found that aged rats are impaired in learning to turn and they seem to prefer straight run. Since this kind of decreased learning ability was speculated to be due to cholinergic deficits, cholinergic antagonists were applied to young rats to test this working hypothesis.

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TRANSIENT IMPAIRMENT OF SPATIAL LEARNING AFTER FOCAL CEREBRAL ISCHEHIA IN RATS SUBJECTED TO RBPEATED MORRIS WATER MAZE TESTS. YOSHIAKI KUMOK'. SABURO SAKAKI-!, SEIJI RATSUD#. MASAHIRO SAKANAKA? AND HIROYUKI YOSHIMURAl, LDeot. of Neurosurcerv and %natomy, and%entral Research Laboratory, Bhime Univ. Sch. of Med., Shicenobu-cho, Ehime 791-02, JaDan. 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 magnocallular nucleus of Meynert (NBM). MCA- or MCA/CCAoccluded rats exhibited only transient disability of place-navigation; the mean latency in MCAor MCA/CCA-occluded rats became close to that of sham-operated rats by 6 to 8 weeks after ischemia. Despite the time-dependent recovery of place-navigation activity in MCA- or MCA/CCAoccluded rats , ChAT neurons in the NBM were fewer on the ischemic side than on the nonischemic 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 MCA- or 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.