Effect of the noncompetitive NMDA antagonists MK-801 and ketamine on the spastic Han-Wistar mutant:: A rat model of excitotoxicity

被引:22
作者
Brunson, KL
Khanna, A
Cromwell, HC
Cohen, RW
机构
[1] Calif State Univ Northridge, Dept Biol, Northridge, CA 91330 USA
[2] Univ Calif Los Angeles, Sch Med, Mental Retardat Res Ctr, Los Angeles, CA 90024 USA
关键词
cerebellum; hippocampus; glutamate receptors; neuroprotection;
D O I
10.1159/000048694
中图分类号
Q [生物科学];
学科分类号
07 [理学]; 0710 [生物学]; 09 [农学];
摘要
The neuroprotective effects of the NMDA antagonists MK-801 and ketamine were analyzed in a mutant strain of Han-Wistar rats which develop neurodegeneration in the hippocampus and cerebellum. Previous experiments have shown that the progressive neuronal degeneration observed in this mutant may be the result of a dysfunctional glutamatergic system. for MK-801 studies, mutants were injected in a chronic paradigm with (+)MK-801 or its weaker acting isomer (-)MK-801 at a dose of 1 mg/kg. Ketamine studies consisted of both acute (50 mg/kg once) and chronic (10 mg/kg multiple times) injection paradigms, MK-801-treated mutants exhibited longer life spans (8-23%) compared to saline-injected mutants. Ketamine-injected mutants in both paradigms also lived slightly longer (6-9%) than the saline mutants. Motor skill deterioration was monitored in an open-field test, and after 50 days of age the MK-801 and ketamine mutants displayed over 20% greater motor skill activity than the saline mutants. In the cerebellum, mutants treated with keta mi ne and both forms of MK-801 had 10-20% more Purkinje cells surviving at 55 days than the saline mutants. Further, the density of CA3c pyramidal hippocampal neurons in ketamine and MK-801-treated mutants as compared to saline mutants appeared to be greater upon qualitative analysis. This study shows that these mutants derive some protective effects from the NMDA antagonists MK-801 and ketamine, confirming glutamate-induced excitotoxicity as a possible cause of neuronal degeneration in this mutant strain of rat. Copyright (C) 2001 S. Karger AG, Basel.
引用
收藏
页码:31 / 40
页数:10
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