Jafari-Sabet Majid
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
Eur J Pharmacol. 2006 Jan 4;529(1-3):122-8. doi: 10.1016/j.ejphar.2005.10.034. Epub 2005 Dec 7.
In the present study, the effects of post-training intra-basolateral amygdala (BLA) injection of an N-methyl-d-aspartate (NMDA) receptor agonist and competitive or noncompetitive antagonists, on memory retention of passive avoidance learning was measured in the presence and absence of physostigmine in rats. Intra-BLA administration of lower doses of NMDA (10(-5) and 10(-4) microg/rat) did not affect memory retention, although higher doses of the drug (10(-3), 10(-2) and 10(-1) microg/rat) increased memory retention. The greatest response was obtained with 10(-1) microg/rat of the drug. The different doses of the competitive NMDA receptor antagonist DL-AP5 (1, 3.2 and 10 microg/rat) and noncompetitive NMDA receptor antagonist MK-801 (0.5, 1 and 2 microg/rat) decreased memory retention in rats dose dependently. Both competitive and noncompetitive NMDA receptor antagonists reduced the effect of NMDA (10(-2) microg/rat). In another series of experiments, intra-BLA injection of physostigmine (2, 3 and 4 microg/rat) improved memory retention. Post-training co-administration of lower doses of NMDA (10(-5) and 10(-4) microg/rat) and physostigmine (1 microg/rat), doses which were ineffective when given alone, significantly improved the retention latency. The competitive and noncompetitive NMDA receptor antagonists, DL-AP5 and MK-801, decreased the effect of physostigmine (2 microg/rat). Atropine decreased memory retention by itself and potentiated the response to DL-AP5 and MK-801. It may be concluded that amygdalar NMDA receptor mechanisms interact with cholinergic systems in the modulation of memory.
在本研究中，在大鼠有或没有毒扁豆碱的情况下，测量了训练后向基底外侧杏仁核（BLA）注射N-甲基-D-天冬氨酸（NMDA）受体激动剂以及竞争性或非竞争性拮抗剂对被动回避学习记忆保持的影响。向BLA内注射较低剂量的NMDA（10^(-5)和10^(-4)微克/大鼠）不影响记忆保持，尽管较高剂量的该药物（10^(-3)、10^(-2)和10^(-1)微克/大鼠）可增强记忆保持。给予10^(-1)微克/大鼠的药物时获得最大反应。不同剂量的竞争性NMDA受体拮抗剂DL-AP5（1、3.2和10微克/大鼠）和非竞争性NMDA受体拮抗剂MK-801（0.5、1和2微克/大鼠）剂量依赖性地降低大鼠的记忆保持。竞争性和非竞争性NMDA受体拮抗剂均降低了NMDA（10^(-2)微克/大鼠）的作用。在另一系列实验中，向BLA内注射毒扁豆碱（2、3和4微克/大鼠）可改善记忆保持。训练后联合给予较低剂量的NMDA（10^(-5)和10^(-4)微克/大鼠）和毒扁豆碱（1微克/大鼠），单独给药时无效的这些剂量可显著延长保持潜伏期。竞争性和非竞争性NMDA受体拮抗剂DL-AP5和MK-801降低了毒扁豆碱（2微克/大鼠）的作用。阿托品自身降低记忆保持，并增强对DL-AP5和MK-801的反应。可以得出结论，杏仁核NMDA受体机制在记忆调节中与胆碱能系统相互作用。
