Departament de Psicobiologia i Metodologia de les Ciencies de la Salut, Institut de Neurociencies, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain.
PLoS One. 2013 Aug 2;8(8):e70584. doi: 10.1371/journal.pone.0070584. Print 2013.
A significant interaction between N-methyl-D-aspartate (NMDA) and muscarinic receptors has been suggested in the modulation of learning and memory processes. The present study further investigates this issue and explores whether d-cycloserine (DCS), a partial agonist at the glycine binding site of the NMDA receptors that has been regarded as a cognitive enhancer, would reverse scopolamine (SCOP)-induced amnesia in two olfactory learning tasks when administered into the prelimbic cortex (PLC). Thus, in experiment 1, DCS (10 µg/site) was infused prior to acquisition of odor discrimination (ODT) and social transmission of food preference (STFP), which have been previously characterized as paradigms sensitive to PLC muscarinic blockade. Immediately after learning such tasks, SCOP was injected (20 µg/site) and the effects of both drugs (alone and combined) were tested in 24-h retention tests. To assess whether DCS effects may depend on the difficulty of the task, in the STFP the rats expressed their food preference either in a standard two-choice test (experiment 1) or a more challenging three-choice test (experiment 2). The results showed that bilateral intra-PLC infusions of SCOP markedly disrupted the ODT and STFP memory tests. Additionally, infusions of DCS alone into the PLC enhanced ODT but not STFP retention. However, the DCS treatment reversed SCOP-induced memory deficits in both tasks, and this effect seemed more apparent in ODT and 3-choice STFP. Such results support the interaction between the glutamatergic and the cholinergic systems in the PLC in such a way that positive modulation of the NMDA receptor/channel, through activation of the glycine binding site, may compensate dysfunction of muscarinic neurotransmission involved in stimulus-reward and relational learning tasks.
N-甲基-D-天冬氨酸（NMDA）和毒蕈碱受体之间的显著相互作用已被认为在学习和记忆过程的调节中起作用。本研究进一步探讨了这一问题，并探讨了 NMDA 受体甘氨酸结合位点的部分激动剂 D-环丝氨酸（DCS）是否会在两个嗅觉学习任务中逆转东莨菪碱（SCOP）诱导的记忆障碍，当将其注入额前皮质（PLC）时。因此，在实验 1 中，DCS（10µg/部位）在获得气味辨别（ODT）和食物偏好的社会传递（STFP）之前被输注，这两个任务先前被认为是对 PLC 毒蕈碱阻断敏感的范式。在学习这些任务后立即注射 SCOP（20µg/部位），并测试两种药物（单独和联合）在 24 小时保留测试中的作用。为了评估 DCS 作用是否取决于任务的难度，在 STFP 中，大鼠在标准的二选一测试（实验 1）或更具挑战性的三选一测试（实验 2）中表达其食物偏好。结果表明，双侧 PLC 内注射 SCOP 明显破坏了 ODT 和 STFP 记忆测试。此外，DCS 单独输注到 PLC 增强了 ODT，但不增强 STFP 保留。然而，DCS 处理逆转了两种任务中的 SCOP 诱导的记忆缺陷，并且这种效应在 ODT 和 3 选择 STFP 中更为明显。这些结果支持 PLC 中谷氨酸能和胆碱能系统之间的相互作用，即 NMDA 受体/通道的正性调制，通过激活甘氨酸结合位点，可能补偿涉及刺激-奖励和关系学习任务的毒蕈碱神经传递功能障碍。
