Pharmacological challenge reveals long-term effects of perinatal phencyclidine on delayed spatial alternation in rats
Pharmacological challenge reveals long-term effects of perinatal phencyclidine on delayed spatial alternation in rats
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DOI：
10.1016/s0278-5846(03)00146-5
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发表时间：
2003-08
影响因子：
5.6
通讯作者：
J. Wiley;Katriona G. Bühler;Kari L. Lavecchia;K. Johnson
中科院分区：
文献类型：
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作者：
J. Wiley;Katriona G. Bühler;Kari L. Lavecchia;K. Johnson
给予N-甲基-d-天冬氨酸(NMDA)拮抗剂苯环利定(PCP)可能会产生类似于在精神分裂症动物模型中观察到的行为变化。本研究旨在研究出生后早期注射五氯苯酚对延迟空间交替作业的后期习得和成绩的影响。延迟空间交替作业是一种对前额叶皮质操作敏感的过程。在研究开始时，我们给交叉养育的雌性大鼠幼鼠在出生后7、9和11天分别皮下注射生理盐水或10 mg/kg五氯苯酚。在出生后34天，大鼠开始进行延迟空间交替训练，每天10次，每次10次，S间隔10次。尽管生理盐水组的准确度显著高于PCP组，但通过PN70，两组都以大致相同的准确度获得了任务。在两组大鼠中，当试验间延迟保持在10 S不变时，使用五氯苯酚和氯胺酮以及多巴胺调节剂苯丙胺的药理学挑战使准确性降低了相似的程度；然而，尼古丁并没有降低两组大鼠的准确性。相比之下，地佐西平(一种高亲和力的NMDA开放通道阻滞剂)在PCP治疗的大鼠中产生了比生理盐水治疗的大鼠更显著的准确性下降。当延迟延长到30 S时，五氯苯酚处理的大鼠的准确性也比生理盐水处理的大鼠降低得更严重。这些结果表明，围产期服用五氯苯酚可能会产生长期的认知改变，这种改变表现为药物挑战和对任务难度的操纵。
Administration of the N-methyl-d-aspartate (NMDA) antagonist phencyclidine (PCP) may produce alterations in behavior that resemble those that have been observed in animal models of schizophrenia. This study was designed to examine the effects of early postnatal injection of PCP on later acquisition and performance of a delayed spatial alternation task, a procedure that is sensitive to manipulations of the prefrontal cortex. At the beginning of the study, we injected cross-fostered female rat pups subcutaneously with either saline or 10 mg/kg PCP on postnatal (PN) days 7, 9, and 11. On PN34, the rats began training in a delayed spatial alternation task consisting of 10 daily trials with a 10-s intertrial interval. Although accuracy improved significantly faster in the saline-treated group than in the PCP-treated group, by PN70, both groups had acquired the task with approximately equal accuracies. Pharmacological challenges with the NMDA antagonists, PCP and ketamine, and with the dopamine modulator, amphetamine, decreased accuracy to a similar extent in both groups of rats when intertrial delays were held constant at 10 s; however, nicotine did not decrease accuracy in either group. In contrast, dizocilpine (a high-affinity NMDA open-channel blocker) produced a more pronounced decrease in accuracy in the PCP-treated rats than in the saline-treated rats. When delays were lengthened to 30 s, PCP also decreased accuracy in the PCP-treated rats to a greater extent than in saline-treated rats. These results suggest that perinatal administration of PCP may produce long-term alterations in cognition that are revealed by pharmacological challenge and manipulation of task difficulty.