杏仁核側底核區被認為在正向與負向情緒相關的學習記憶中扮演關鍵性的角色。我們以此為基礎，證明在提取古柯鹼場地制約偏好或被動逃避反應後，隨即在杏仁核側底核區注射利多卡因，會在後續的測試中選擇性地減少被提取的記憶表現強度。相反的，單獨只在杏仁核側底核區施打利多卡因不會影響記憶的表現。我們企圖去驗證過去的假設，即未被提取的記憶絕對不可能進入不穩定且易受修改的狀態之下。部份的老鼠被訓練並學會古柯鹼場地制約偏好與被動逃避反應，當其中一個已學會的記憶被提取之後，立即在杏仁核側底核區施打利多卡因，並且在隨後的再測試中測量記憶的表現，以了解記憶維持的情況。我們證明在被動逃避反應記憶被提取之後，馬上在杏仁核側底核區注射利多卡因會削弱被動逃避反應與古柯鹼場地制約偏好在後續再測試的表現。同樣地，在古柯鹼場地制約偏好記憶被提取之後，隨即在杏仁核側底核區注射利多卡因會減低被動逃避反應與古柯鹼場地制約偏好在後續再測試的表現。我們認為提取一個記憶可以使其他儲存在相關腦區的記憶變得易受改變。此外，許多研究證明某些特定的細胞內訊息傳導路徑會參與記憶的再穩固歷程，然而，在這眾多的訊息傳導路徑中，又以分裂原活化蛋白激（mitogen-activated protein kinase, MAPK）在突觸可塑性與記憶形成中所扮演的角色最常被研究。先前，我們證明U0126（為MAPK/ERK 激的抑制劑）會干擾古柯鹼場地制約偏好的再穩固歷程，且在初步的研究結果中，我們發現活化被動逃避反應記憶後，立即在杏仁核側底核區施打U0126可以有效地損害後續被動逃避反應記憶的提取。U0126與利多卡因的研究結果是相反的，我們發現不論是哪一個記憶被提取後，馬上在杏仁核側底核區施打U0126不會損害古柯鹼場地制約偏好與被動逃避反應記憶。

Basolateral nuclei of amygdala (BLA) are thought to play a critical role in mediating both positive and negative emotion-supported learning and memory. We hereby demonstrate that intra-BLA lidocaine infusion immediately after the reactivation of cocaine-induced conditioned place preference (CPP) or passive avoidance (PA) memory selectively diminishes the expression magnitude of the reactivated memory in subsequent tests. In contrast, intra-BLA infusion of lidocaine alone does not affect the memory expression. We attempt to test the hypothesis that a non-reactivated memory can never return to a labile state susceptible to modification. Some mice were trained to acquire both cocaine-induced CPP and PA memory. Intra-BLA lidocaine infusion was given immediately after the reactivation of one of the acquired memory, and the performance of these memories was measured in subsequent retests for the maintenance of these memories. Here we show that intra-BLA lidocaine infusion immediately following the reactivation of passive avoidance memory diminishes the performance of both PA and cocaine-induced CPP memories in subsequent retests. Likewise, intra-BLA lidocaine infusion immediately following the reactivation of cocaine-induced CPP memory diminishes the performance of both cocaine-induced CPP and PA memories in subsequent retests. We conclude that reactivation of one memory can make the other storage-related memories susceptible to modification. In addition, numerous studies have demonstrated that specific intracellular signaling pathways are involved in the reconsolidation of various memories. Of these numerous pathways, one in particular has been vigorously studied for the role in synaptic plasticity and memory formation, the mitogen-activated protein kinase (MAPK) pathway. Previously, we demonstrated that U0126, an inhibitor of MAPK/ERK kinase (MEK), disrupted the reconsolidation of cocaine-induced CPP memory. In our preliminary results, we found that intra-BLA infusion with U0126 after the reactivation of passive avoidance memory effectively impaired subsequent retrieval of this memory. In contrast with the results of lidocaine, we found that injection of U0126 into the BLA impaired neither cocaine-induced CPP nor PA memory regardless which memory was reactivated.

1. Abel T, Lattal KM (2001) Molecular mechanisms of memory acquisition, consolidation and retrieval. Curr Opin Neurobiol 11:180-187.
2. Burns LH, Everitt BJ, Robbins TW. Differential effects of excitotoxic lesions of the basolateral amygdale, ventral subiculum and medial prefrontal cortex on responding with conditioned reinforcement and locomotor activity potentiated by intra-accumbens infusions of d-amphetamine. Behav Brain Res 55:167-183 (1993).
3. Calandreaul, L., Desmedt, A., Decorte, L., and Jaffard, R. A different recruitment of the lateral and basolateral nuclei of amygdala promotes contextual or elemental conditioned association in Pavlovian fear conditioning. Learn. Mem. 12: 383-388 (2005).
4. Cammarota, M., Bevilaqua, L. R.M., Medina, J. H., and Izquierdo, I. Retrieval does not induce reconsolidation of inhibitory avoidance memory. Learn. Mem. 11: 572-578 (2007).
5. Cestari, V., Costanzi, M., Castellano, C., and Rossi-Arnaud, C. A role for ERK2 in reconsolidation of fear memories in mice. Neurobiol. Learn. Mem. 86: 133-143 (2006).
6. Davis, J. A., and Gould, T. J. The effects of DHBE and MLA on nicotine-induced enhancement of contextual fear conditioning in C57BL/6 mice. Psychopharmacol. 184: 345-352 (2006).
7. Dudai Y. Molecular bases of long-term memories: a question of persistence. Curr Opin Neurobiol 12:211-216 (2002).
8. Dudai Y, Eisenberg M. Rites of passage of the engram: reconsolidation and the lingering consolidation hypothesis. Neuron 44:93-100 (2004).
9. Duvarci, S., Nader, K., and LeDoux, J. E. Activation of extracellular signal-regulated kinase－mitogen-activated protein kinase cascade in the amygdala was required for memory reconsolidation of auditory fear conditioning. Eur. J. Neurosci. 21: 283-289 (2005).
10. Lai, Y-T., Fan, H-Y., Cherng, C. G., Chiang, C-Y., Kao, G-S., and Yu, L. Activation of amygdaloid PKC pathway is necessary for conditioned cues-provoked cocaine memory performance. Neurobiol. Learn. Mem. 90: 164-170 (2008).
11. Lai, Y-T., Cherng, C. G., Chiang, C-Y., Chang, W-T., Lin, P-S., Lee, Y-S., and Yu, L. Inhibition of PKA and ERK pathways in basolateral amygdala impairs reconsolidation of the cocaine memory. In preparation.
12. Laurent, V. and Westbrook, R. F. Distinct contributions of the basolateral amygdala and the medial prefrontal cortex to learning and relearning extinction of context conditioned fear. Learn. Mem. 15(9): 657-66 (2008).
13. Lee, S-H., Choi, J-H., Lee, N., Lee, H-R., Kim, J-I., Yu, N-K., Choi, S-L., Lee, S-H., Kim, H., and Kaang, B-K. Synaptic protein degradation underlies destabilization of retrieved fear memory. Science 319:1253-1256 (2008).
14. Lee JL, Milton AL, Everitt BJ. Cue-induced cocaine seeking and relapse are reduced by disruption of drug memory reconsolidation. J Neurosci 26:5881-5887 (2006).
15. Lewis, D. J. Psychobiology of active and inactive memory. Psychol. Bull. 86(5): 1054-1083 (1979).
16. Nader, K., Schafe, G. E., and LeDoux, J. E. Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406: 722-726 (2000).
17. Nader K, Schafe GE, LeDoux JE. The labile nature of consolidation theory. Nat Rev Neurosci 1: 216-219 (2000).
18. Nader, K. Memory traces unbound. Trends in Neurosci. 26(2): 65-72 (2003).
19. Rossato, J. I., Bonini, J. S., Coitinho, A. S., Vianna, M. R. M., Medina, J. H., Cammarota, M., and Izquierdo, I. Retrograde amnesia induced by drugs acting on different molecular systems. Behav. Neurosci. 118(3): 563-568 (2004).
20. Sahand, P., and Westbrook, R. F. The circuit of fear. Nature 454: 589-90 (2008).
21. Sakata, Y., Chida, R., Ishige, K., Edagawa, Y., Tanano, T., and Ito, Y. Effect of a nutritive-tonic drink on scopolamine-induced memory impairment in mice. Biol. Pharm. Bull. 28(10): 1886-1891 (2005).
22. Sara SJ. Retrieval and reconsolidation: toward a neurobiology of remembering. Learn Mem 7:73-84 (2000).
23. Troson, N. C., and Taylor, J. R. Molecular mechanisms of memory reconsolidation. Nature Reviews 8:262-273 (2007).