Lewis Michael C, Gould Thomas J
Temple University Neuroscience Program, Department of Psychology, Weiss Hall, Temple University, 1701 N 13th St., Philadelphia, PA 19122, USA.
Eur J Neurosci. 2004 Aug;20(3):818-26. doi: 10.1111/j.1460-9568.2004.03531.x.
Much of the research examining the biological basis for long-term memories has focused on mechanisms that support the formation of conditioned associations. Less information is available on biological mechanisms which underlie processes that modify the strength of conditioned associations. Latent inhibition is a phenomenon by which pre-exposure to a to-be-conditioned stimulus (CS) weakens subsequent conditioning of that CS to an unconditioned stimulus (US). Here we report that latent inhibition of cued fear conditioning is dependent on NMDA receptor activation. MK-801 (1 mg/kg), an NMDA receptor antagonist, abolished latent inhibition of cued fear conditioning. This dose of MK-801 administered before training did not disrupt cued fear conditioning. Conversely, anisomycin (150 mg/kg), a protein synthesis inhibitor, had no effect on latent inhibition of cued fear conditioning when administered 20 min before, immediately after, or 2, 4, 6, or 8 h after CS pre-exposure. Furthermore, continuous anisomycin administration (50 mg/kg, administered every 2 h for 6 h starting 20 min prior to pre-exposure) did not disrupt latent inhibition of cued fear conditioning. In addition, anisomycin had no effect on a long-lasting version of latent inhibition of cued fear conditioning that was maintained over a 7-day interval. Anisomycin administered before training, however, disrupted learning of the CS-US association. These findings suggest that latent inhibition of cued fear conditioning is a long-lasting NMDA receptor-dependent process that can develop during the inhibition of protein synthesis.
许多研究长期记忆生物学基础的研究都集中在支持条件性联想形成的机制上。关于调节条件性联想强度的过程所基于的生物学机制，目前了解较少。潜伏抑制是一种现象，即预先暴露于待条件化刺激（CS）会削弱该CS随后与非条件刺激（US）形成的条件反射。在此我们报告，线索性恐惧条件反射的潜伏抑制依赖于NMDA受体激活。NMDA受体拮抗剂MK-801（1毫克/千克）消除了线索性恐惧条件反射的潜伏抑制。在训练前给予该剂量的MK-801不会破坏线索性恐惧条件反射。相反，蛋白质合成抑制剂茴香霉素（150毫克/千克）在CS预先暴露前20分钟、暴露后立即、或暴露后2、4、6或8小时给予时，对线索性恐惧条件反射的潜伏抑制没有影响。此外，持续给予茴香霉素（50毫克/千克，在预先暴露前20分钟开始，每2小时给药一次，共6小时）不会破坏线索性恐惧条件反射的潜伏抑制。另外，茴香霉素对在7天间隔内维持的线索性恐惧条件反射的长期潜伏抑制版本没有影响。然而，在训练前给予茴香霉素会破坏CS-US联想的学习。这些发现表明，线索性恐惧条件反射的潜伏抑制是一个长期的、依赖NMDA受体的过程，它可以在蛋白质合成受到抑制时形成。
