Sharma A C, Kulkarni S K
Department of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Methods Find Exp Clin Pharmacol. 1991 Apr;13(3):155-9.
The phenomenon of long-term potentiation (LTP) formation in hippocampal and neocortical brain areas has been suggested as a mechanism for learning and memory where NMDA-receptors play a significant role. Various agonists have been proposed to facilitate LTP and thereby learning and memory. Competitive and non-competitive antagonists of NMDA-receptors block LTP formation and produce attentional or acquisition deficit in animals. A series of experiments were carried out with noncompetitive NMDA antagonists, MK-801 (10-100 micrograms/kg) and ketamine (1-10 mg/kg), in passive avoidance step-down task paradigm in mice. MK-801 showed complete disruption of acquisition at higher doses, while very low doses showed improvement in retention. MK-801 showed additive or potentiating influence on scopolamine-induced deficits. The results of the interaction of NMDA antagonists with scopolamine provide a basis for the speculation that cholinergic- and NMDA-antagonism may play a hand in hand role in short-term memory disturbances in passive avoidance step-down task paradigm in mice.
海马体和新皮质脑区中长时程增强（LTP）形成的现象被认为是一种学习和记忆机制，其中N-甲基-D-天冬氨酸（NMDA）受体起着重要作用。人们提出了各种激动剂来促进LTP，从而促进学习和记忆。NMDA受体的竞争性和非竞争性拮抗剂会阻断LTP的形成，并在动物身上产生注意力或习得缺陷。在小鼠被动回避跳台任务范式中，使用非竞争性NMDA拮抗剂MK-801（10-100微克/千克）和氯胺酮（1-10毫克/千克）进行了一系列实验。高剂量的MK-801显示习得完全被破坏，而极低剂量则显示记忆保持有所改善。MK-801对东莨菪碱诱导的缺陷有累加或增强作用。NMDA拮抗剂与东莨菪碱相互作用的结果为以下推测提供了依据：胆碱能和NMDA拮抗作用可能在小鼠被动回避跳台任务范式中的短期记忆障碍中共同起作用。
