Spatial memory deficits induced by perinatal treatment of rats with PCP and reversal effect of D-serine
Spatial memory deficits induced by perinatal treatment of rats with PCP and reversal effect of D-serine
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DOI：
10.1038/sj.npp.1300394
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发表时间：
2004-06-01
影响因子：
7.6
通讯作者：
Pouzet, B
中科院分区：
文献类型：
--
作者：
Andersen, JD;Pouzet, B
有人建议，围产期治疗与非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂苯环己哌啶（PCP）诱导大鼠边缘系统和皮质结构的短暂神经变性。由于这些结构的功能障碍与精神分裂症患者的认知缺陷有关，我们研究了亚慢性治疗与PCP在围产期大鼠在成年期的空间参考，逆转，空间工作记忆使用Morris水迷宫任务的影响。此外，我们还研究了D-丝氨酸的作用，它与治疗精神分裂症患者的认知缺陷具有临床相关性。我们的目标是建立一个神经发育模型，对精神分裂症患者的认知功能障碍具有预测有效性。雄性和雌性Sprague-Dawley大鼠用生理盐水或PCP（8.7 mg/kg s.c.）在出生后第7、9和11天，研究了对成年期行为的长期影响。PCP处理的雄性大鼠在空间参考记忆任务中轻微受损，但在反转和空间工作记忆任务中严重受损。雌性大鼠未受到该处理的显著影响。这种认知缺陷通过D-丝氨酸的长期治疗逆转。我们认为，该模型模拟了精神分裂症患者的认知缺陷，可能适合于筛选公认的抗精神病药物治疗这些认知缺陷。
It has been suggested that perinatal treatment with the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (PCP) induces transient neurodegeneration in the limbic and cortical structures of rats. Since dysfunction of these structures is associated with cognitive deficits in patients with schizophrenia, we studied the effects of subchronic treatment with PCP in perinatal rats with respect to spatial reference, reversal, and spatial working memories using the Morris water maze task in adulthood. In addition, we investigated the effect of D-serine, which has clinical relevance for the treatment of cognitive deficits in patients with schizophrenia. Our goal was to develop a neurodevelopmental model with predictive validity for the cognitive dysfunction described in patients with schizophrenia. Male and female Sprague-Dawley rats were treated with either saline or PCP (8.7 mg/kg s.c.) on days 7, 9, and 11, postnatal, and the long-term behavioral effects were investigated in adulthood. Male PCP-treated rats were slightly impaired during the spatial reference memory task, but strongly impaired during the reversal and spatial working memory tasks. Female rats were not significantly affected by this treatment. This cognitive deficit was reversed by chronic treatment with D-serine. We suggest that this model mimics some of the cognitive deficits of patients with schizophrenia and might be appropriate for the screening of putative antipsychotic agents for the treatment of these cognitive deficits.