Kim M, McGaugh J L
Center for the Neurobiology of Learning and Memory, University of California, Irvine 92717.
Brain Res. 1992 Jul 10;585(1-2):35-48. doi: 10.1016/0006-8993(92)91188-k.
These experiments examined the effects of intra-amygdala injections of NMDA receptor antagonists on the acquisition and retention of inhibitory avoidance. In Expt. I, rats received bilateral intra-amygdala injections of the NMDA antagonists D,L-AP5 (1-10 micrograms), D-AP5 (0.03-1 micrograms), CPP (0.125 or 0.375 microgram), or MK-801 (0.2 or 0.5 microgram) prior to training in a continuous multiple-trial inhibitory avoidance (CMIA) task. Acquisition of the task was not significantly affected by any of the drug injections. In contrast, all three competitive antagonists, D,L-AP5, D-AP5 and CPP, produced dose-dependent impairment of 48 h retention performance. Although the MK-801 injections did not significantly impair retention performance, the retention scores of the 0.5 microgram MK-801 group were bimodally distributed, indicating retention impairment in a subgroup of the animals given that dose. Intra-amygdala injections of 3 or 10 micrograms D,L-AP5 did not affect footshock sensitivity (Expt. II) or locomotor activity (Expt. III) and their retention-impairing effects were not due to induction of state dependency (Expt. IV). The retention-impairing effects of intra-amygdala injections of NMDA antagonists were not due to diffusion of the drugs dorsally: injections of 1 microgram D-AP5 into the striatal area directly above the amygdala impaired acquisition but not retention performance (Expt. V). The retention-impairing effects of 1 microgram D-AP5 or 0.5 microgram MK-801 were attenuated by giving additional training to the animals shortly after receiving intra-amygdala injections (Expt. VI). The implications of these findings for hypotheses concerning amygdala function in learning and memory are discussed.
这些实验研究了杏仁核内注射NMDA受体拮抗剂对抑制性回避学习和记忆保持的影响。在实验I中，大鼠在连续多次试验抑制性回避（CMIA）任务训练前，双侧杏仁核内注射NMDA拮抗剂D,L-AP5（1 - 10微克）、D-AP5（0.03 - 1微克）、CPP（0.125或0.375微克）或MK-801（0.2或0.5微克）。任务的习得未受到任何药物注射的显著影响。相比之下，所有三种竞争性拮抗剂D,L-AP5、D-AP5和CPP均产生了剂量依赖性的48小时记忆保持性能损害。虽然MK-801注射未显著损害记忆保持性能，但0.5微克MK-801组的记忆保持分数呈双峰分布，表明给予该剂量的动物亚组存在记忆保持损害。杏仁核内注射3或10微克D,L-AP5不影响足底电击敏感性（实验II）或运动活动（实验III），其记忆保持损害作用并非由状态依赖性诱导所致（实验IV）。杏仁核内注射NMDA拮抗剂的记忆保持损害作用并非由于药物向背侧扩散：在杏仁核上方的纹状体区域注射1微克D-AP5损害习得但不损害记忆保持性能（实验V）。在杏仁核内注射后不久对动物进行额外训练，可减轻1微克D-AP5或0.5微克MK-801的记忆保持损害作用（实验VI）。讨论了这些发现对有关杏仁核在学习和记忆中功能假说的意义。
