Department of Psychology, Durham University, South Road, Durham DH1 3LE, UK; Centre for Learning and Memory Processes, Durham University, Durham, UK; Department of Psychology, Koç University, Rumelifeneri yolu, Sarıyer, 34450, Istanbul, Turkey(1).
Department of Psychology, Durham University, South Road, Durham DH1 3LE, UK; Centre for Learning and Memory Processes, Durham University, Durham, UK.
Neurobiol Learn Mem. 2019 May;161:57-62. doi: 10.1016/j.nlm.2019.03.006. Epub 2019 Mar 19.
NMDA receptor-dependent synaptic plasticity has been proposed to be important for encoding of memories. Consistent with this hypothesis, the non-competitive NMDA receptor antagonist, MK-801, has been found to impair performance on tests of memory. Interpretation of some of these findings has, however, been complicated by the fact that the drug-state of animals has differed during encoding and tests of memory. Therefore, it is possible that MK-801 may result in state-dependent retrieval or expression of memory rather than actually impairing encoding itself. We tested this hypothesis in mice using tests of object recognition memory with a 24-hour delay between the encoding and test phase. Mice received injections of either vehicle or MK-801 prior to the encoding phase and the test phase. In Experiment 1, a low dose of MK-801 (0.01 mg/kg) impaired performance when the drug-state (vehicle or MK-801) of mice changed between encoding and test, but there was no significant effect of MK-801 on encoding. In Experiment 2, a higher dose of MK-801 (0.1 mg/kg) failed to impair object recognition memory when mice received the drug prior to both encoding and test compared to mice that received vehicle. MK-801 did not affect object exploration, but it did induce locomotor hyperactivity at the higher dose. These results suggest that some previous demonstrations of MK-801 effects may reflect a failure to express or retrieve memory due to the state-dependency of memory rather than impaired encoding of memory.
NMDA 受体依赖性突触可塑性被认为对记忆的编码很重要。与这一假设一致，非竞争性 NMDA 受体拮抗剂 MK-801 已被发现会损害记忆测试的表现。然而，这些发现的一些解释受到了药物状态在编码和记忆测试期间不同的事实的复杂化。因此，MK-801 可能导致记忆的状态依赖性检索或表达，而不是实际上损害编码本身。我们在小鼠中使用物体识别记忆测试来检验这一假设，该测试在编码和测试阶段之间有 24 小时的延迟。在编码阶段之前，小鼠接受了载体或 MK-801 的注射，然后在测试阶段进行注射。在实验 1 中，当小鼠在编码和测试之间的药物状态（载体或 MK-801）发生变化时，低剂量的 MK-801（0.01mg/kg）会损害表现，但 MK-801 对编码没有显著影响。在实验 2 中，与接受载体的小鼠相比，当小鼠在编码和测试之前都接受高剂量的 MK-801（0.1mg/kg）时，它未能损害物体识别记忆。MK-801 不会影响物体探索，但它确实会在高剂量时引起运动过度活跃。这些结果表明，以前对 MK-801 效应的一些证明可能反映了由于记忆的状态依赖性而导致记忆的表达或检索失败，而不是记忆编码受损。
