Guscott Martin R, Clarke Hannah F, Murray Fraser, Grimwood Sarah, Bristow Linda J, Hutson Peter H
Merck, Sharp and Dohme, The Neuroscience Research Centre, Behavioural Neuroscience, Terlings Park, Harlow CM20 2QR, UK.
Eur J Pharmacol. 2003 Aug 29;476(3):193-9. doi: 10.1016/s0014-2999(03)02182-4.
It is well established that the NMDA receptor antagonists block hippocampal long-term potentiation and impair acquisition in the Morris watermaze task, although the role of individual NMDA receptor subtypes is largely unknown. In the present study, we compared the effects of (+/-)-CP-101,606, an antagonist selective for NMDA receptor NR1/NR2B subunit-containing receptors and the nonselective NMDA receptor antagonist MK-801, on acquisition in the Morris watermaze. Male hooded Lister rats were given 4 trials/day to find a fixed hidden platform submerged beneath the opaque water of the Morris watermaze. Twenty-four hours after the last acquisition trial, a 'probe trial' was conducted to assess the rat's spatial memory for the location of the hidden platform. Those rats treated with MK-801 (0.1 mg/kg, i.p.) 60 min prior to the acquisition and probe trials took significantly longer to find the hidden platform during training and spent significantly less time searching the platform's location during the probe trial than vehicle-treated rats. In contrast, 60-min pretreatment with (+/-)-CP-101,606 (60 mg/kg, p.o.), a dose that fully occupied hippocampal NR1/NR2B subunit-containing receptors, as determined by ex vivo NMDA receptor-specific [3H]ifenprodil binding immediately following watermaze experiments, had no effect on acquisition or the probe trial. These results suggest that antagonists selective for NR1/NR2B subunit-containing receptors may not impair spatial memory in rats in the Morris watermaze.
虽然单个NMDA受体亚型的作用在很大程度上尚不清楚，但NMDA受体拮抗剂可阻断海马体的长时程增强效应并损害莫里斯水迷宫任务中的学习能力，这一点已得到充分证实。在本研究中，我们比较了对含NMDA受体NR1/NR2B亚基的受体具有选择性的拮抗剂(+/-)-CP-101,606和非选择性NMDA受体拮抗剂MK-801对莫里斯水迷宫学习能力的影响。给雄性带帽利斯特大鼠每天进行4次试验，以找到隐藏在莫里斯水迷宫不透明水下的固定平台。在最后一次学习试验24小时后，进行一次“探索试验”，以评估大鼠对隐藏平台位置的空间记忆。在学习试验和探索试验前60分钟接受MK-801（0.1mg/kg，腹腔注射）处理的大鼠，在训练过程中找到隐藏平台的时间明显更长，并且在探索试验中搜索平台位置的时间明显少于接受溶剂处理的大鼠。相比之下，(+/-)-CP-101,606（60mg/kg，口服）进行60分钟预处理（根据水迷宫实验后立即进行的离体NMDA受体特异性[3H]ifenprodil结合测定，该剂量可完全占据含海马体NR1/NR2B亚基的受体）对学习或探索试验没有影响。这些结果表明，对含NR1/NR2B亚基的受体具有选择性的拮抗剂可能不会损害大鼠在莫里斯水迷宫中的空间记忆。
