期刊
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
卷 77, 期 1, 页码 183-190出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2003.10.013
关键词
maple syrup urine disease; alpha-ketoisocaproic acid; alpha-keto-beta-methylvaleric acid; alpha-ketoisovaleric acid; rat behavior
Learning disability is a common feature of patients affected by maple syrup urine disease (MSUD). However, the pathomechanisms underlying learning deficit in this disorder are poorly known. In the present study, we investigated the effect of acute administration of the alpha-keto acids accumulating in MSUD into the hippocampus on the behavior of rats in the open field and in the inhibitory avoidance tasks. Adult male Wistar rats received intrahippocampal injections of alpha-ketoisocaproic acid (KIC, 8 mumol), alpha-ketoisovaleric acid (KIV, 5 mumol), alpha-keto-beta-methylvaleric acid (KMV, 5 mumol), or NaCl (8 mumol) (controls) immediately after or 10 min before training. Testing session was performed 24 h later. Posttraining administration of the keto acids had no effect on learning in the open-field task. In contrast, pretraining administration of KIV and KMV impaired habituation in the open field. Similarly, pretraining administration of KIC, KIV, and KMV affected rat performance in the inhibitory avoidance task, suggesting disruption of acquisition. The results indicate that the alpha-keto acids accumulating in MSUD induce learning deficits in aversive and nonaversive tasks. We therefore suggest that these findings may be related to the psychomotor delay/mental retardation observed in MSUD, and may indicate the contribution of increased brain concentrations of these organic acids to the pathophysiology of the neurological dysfunction of MSUD patients. (C) 2003 Elsevier Inc. All rights reserved.
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