Wass Caroline, Archer Trevor, Pålsson Erik, Fejgin Kim, Klamer Daniel, Engel Jörgen A, Svensson Lennart
Department of Pharmacology, The Sahlgrenska Academy at Göteborg University, Sweden.
Behav Brain Res. 2006 Jul 15;171(1):147-53. doi: 10.1016/j.bbr.2006.03.036. Epub 2006 May 4.
Cognitive deficits of schizophrenia constitute a disabling part of the disease predicting treatment success as well as functional outcome. Phencyclidine (PCP), a non-competitive NMDA receptor antagonist was used to model schizophrenic cognitive dysfunctions of learning and memory using the Morris water maze paradigm for reference memory. In experiment 1 male Sprauge-Dawley rats were acutely administered PCP (0.5, 1.0 and 2.0 mg/kg s.c.) before the first swim session on each of the four acquisition days. Probe test for reference memory was performed 2 days after the last acquisition day; the first probe without drug treatment to assess reference memory and a second probe with prior drug treatment to control for state dependency effects of PCP. In experiment 2 the effects of pre-treatment (10 min before PCP) with the nitric oxide synthase inhibitor, L-NAME (10 mg/kg s.c.), on the PCP (2 mg/kg)-induced spatial memory deficit was evaluated in the Morris water maze paradigm for reference memory. The results showed that PCP in a dose of 2 mg/kg disrupts spatial learning as estimated by prolonged search time to find platform during acquisition as well as the reference memory test as measured by less time spent in target quadrant during probe trial. No state dependency effects of PCP were found. Pre-treatment with L-NAME completely reversed the PCP-induced disruption of acquisition learning. The reference memory disruption was, however, not completely restored as measured by probe trial.
精神分裂症的认知缺陷是该疾病导致残疾的一部分，它预示着治疗成功与否以及功能结局。苯环己哌啶（PCP）是一种非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，被用于以莫里斯水迷宫范式进行参考记忆，来模拟精神分裂症患者学习和记忆方面的认知功能障碍。在实验1中，雄性斯普拉格-道利大鼠在四个训练日中每个训练日的首次游泳训练前，分别急性注射PCP（0.5、1.0和2.0毫克/千克，皮下注射）。在最后一个训练日后2天进行参考记忆的探针测试；第一次探针测试不进行药物处理以评估参考记忆，第二次探针测试在先前药物处理后进行，以控制PCP的状态依赖性效应。在实验2中，在莫里斯水迷宫范式进行参考记忆测试时，评估一氧化氮合酶抑制剂L-硝基精氨酸甲酯（L-NAME，10毫克/千克，皮下注射）预处理（在注射PCP前10分钟）对PCP（2毫克/千克）诱导的空间记忆缺陷的影响。结果表明，2毫克/千克剂量的PCP会破坏空间学习，这可通过训练期间寻找平台的搜索时间延长来估计，同时也会破坏参考记忆测试，这可通过探针试验期间在目标象限花费的时间减少来衡量。未发现PCP的状态依赖性效应。L-NAME预处理完全逆转了PCP诱导的训练学习破坏。然而，通过探针试验测量，参考记忆破坏并未完全恢复。
