Kim J J, DeCola J P, Landeira-Fernandez J, Fanselow M S
Department of Psychology, University of California, Los Angeles 90024.
Behav Neurosci. 1991 Feb;105(1):126-33. doi: 10.1037//0735-7044.105.1.126.
The role of N-methyl-D-aspartate (NMDA) receptors in Pavlovian fear conditioning was examined using the NMDA antagonist DL-2-amino-5-phosphonovaleric acid (APV). Either APV (5 micrograms/rat) or saline was administered before the training phase, the testing phase, or both. APV completely blocked acquisition but not expression of fear conditioning. The L enantiomer of APV did not affect the acquisition of conditional fear. To separate encoding from consolidation processes, APV was administered either before or immediately after the footshock unconditional stimulus (US) during the training phase. The results indicate that APV must be present during the US to produce its effects on fear conditioning. The behavioral effect of the drug is not due to analgesic action because APV did not alter pain sensitivity. The data suggest that NMDA receptors are critical for the acquisition but not expression of fear conditioning. These effects on fear conditioning are parallel to the in vitro effects of APV on the acquisition but not expression of long-term potentiation (LTP) and suggest that endogenously generated NMDA-dependent LTP participates in the neural plasticity underlying fear conditioning.
使用N-甲基-D-天冬氨酸（NMDA）拮抗剂DL-2-氨基-5-磷酸戊酸（APV）研究了NMDA受体在巴甫洛夫式恐惧条件反射中的作用。在训练阶段、测试阶段或两个阶段之前，分别给予APV（5微克/大鼠）或生理盐水。APV完全阻断了恐惧条件反射的获得，但不影响其表达。APV的L型对条件性恐惧的获得没有影响。为了区分编码和巩固过程，在训练阶段，在足底电击无条件刺激（US）之前或之后立即给予APV。结果表明，APV必须在US期间存在才能对恐惧条件反射产生影响。该药物的行为效应并非由于镇痛作用，因为APV并未改变疼痛敏感性。数据表明，NMDA受体对恐惧条件反射的获得至关重要，但对其表达并不重要。这些对恐惧条件反射的影响与APV在体外对长期增强（LTP）的获得而非表达的影响相似，表明内源性产生的NMDA依赖性LTP参与了恐惧条件反射背后的神经可塑性。
