Lyford G L, Gutnikov S A, Clark A M, Rawlins J N
University of Oxford, Department of Experimental Psychology, U.K.
Neuropsychologia. 1993 Oct;31(10):1079-98. doi: 10.1016/0028-3932(93)90034-w.
Two series of experiments using rats assessed the effects of intraventricular administration of the NMDA antagonist AP5 on performance of non-spatial working memory tasks. The first series used a continuous delayed non-matching to sample (DNMS) design; the second series used a discrete trial delayed matching to sample (DMS) design. Performance was assessed at retention intervals ranging from approximately 5 to 90 sec. The subjects had acquired the behavioural tasks before drug testing commenced. In the DNMS series, minipumps containing vehicle, 5, 10 or 15 nM D-AP5 were implanted. Every 10 days, each rat's minipump was removed and replaced with a fresh pump containing a new drug dose in a counterbalanced design, so that all rats were tested under all four conditions. There were no drug effects on performance at any retention interval. In the DMS series, there were three different basic task variants. Minipumps filled either with 15 mM D-AP5 or vehicle solution were implanted. Vehicle rats performed at approximately pre-operative levels; AP5 rats were impaired only on task variants using repeated stimulus presentations within session. There was no interaction between retention interval and drug treatment. This pattern of results closely resembles that seen following hippocampectomy or fornicotomy, as would be expected if this drug, administered intraventricularly, selectively affected hippocampal function.
两个使用大鼠的实验系列评估了脑室内注射N-甲基-D-天冬氨酸（NMDA）拮抗剂AP5对非空间工作记忆任务表现的影响。第一个系列采用连续延迟样本匹配（DNMS）设计；第二个系列采用离散试验延迟样本匹配（DMS）设计。在大约5至90秒的保持间隔内评估表现。在药物测试开始前，实验对象已经掌握了行为任务。在DNMS系列中，植入了含有载体、5、10或15 nM D-AP5的微型泵。每10天，取出每只大鼠的微型泵，并用一个含有新药物剂量的新鲜泵以平衡设计进行替换，以便所有大鼠在所有四种条件下接受测试。在任何保持间隔下，药物对表现均无影响。在DMS系列中，有三种不同的基本任务变体。植入了填充有15 mM D-AP5或载体溶液的微型泵。载体组大鼠的表现约为术前水平；AP5组大鼠仅在使用会话内重复刺激呈现的任务变体上受损。保持间隔和药物治疗之间没有相互作用。这种结果模式与海马切除或穹窿切断术后所见的模式非常相似，如果脑室内注射这种药物选择性地影响海马功能，这是可以预期的。
