儘管過去認為學習與記憶需依賴完整意識，近期研究指出，在意識受限狀態下仍可能產生內隱記憶，如古典制約。然而在麻醉這種意識受限狀態下，是否能完成恐懼消除的學習，目前仍缺乏更多行為上的研究證據。在動物麻醉經常使用的藥物右美托嘧啶是一種的 α2 腎上腺素受體致效劑，能抑制藍斑核的正腎上腺素釋放，進而導致意識改變。本研究即以此藥物建立大鼠的麻醉模型，探討在非清醒狀態下是否仍可進行恐懼制約消除的學習。共五個行為實驗，分別探討：(1) 麻醉下是否可建立視覺線索恐懼制約、(2) 麻醉下是否可消除麻醉時建立的恐懼制約、(3) 麻醉下是否可消除清醒時建立的恐懼制約、(4) 周邊注射腎上腺素是否促進消除學習，以及 (5) 前額葉下邊緣皮質區域的 β - 腎上腺素受體是否參與此促進效果。結果發現，大鼠在右美托嘧啶麻醉下，可以學會恐懼制約與消除；若周邊注射腎上腺素，可有效促進麻醉下的恐懼消除學習。而且在下邊緣皮質區域內注射 β - 腎上腺素受體拮抗劑，可以阻斷周邊注射腎上腺素的促進效果，顯示此區域的 β - 腎上腺素受體為恐懼消除的關鍵機制。本研究結果拓展了意識與學習關係的理解，並提供藥物結合行為療法的新可能，未來有潛力應用於提升暴露療法在臨床上治療焦慮與恐懼症的成效。

Past studies suggested that learning requires full awareness, but recent research shows some types of memory, like fear conditioning, can occur under reduced awareness. This study used dexmedetomidine, a selective α2-adrenergic receptor agonist that lowers norepinephrine release, to create an anesthesia model in rats. We tested whether rats could form fear and extinction memories under anesthesia. In the pilot experiment, rats indeed acquired visually-cued fear conditioning under anesthesia. In Experiments 1 and 2, extinction training was also given under anesthesia—either for fear learned under anesthesia or while awake. However, extinction under anesthesia required more sessions to reduce fear. Experiment 3 tested whether epinephrine could enhance extinction under anesthesia. Rats that received epinephrine showed faster fear reduction than controls. In Experiment 4, a β-adrenergic receptor antagonist propranolol was injected into the infralimbic cortex to block the epinephrine effect. Our results show that fear extinction can occur under anesthesia. In addition, norepinephrine can facilitate this extinction learning, and the β-adrenergic receptor in the infralimbic cortex plays a key role. These findings expand our understanding of learning under reduced awareness and suggest a new approach to improve exposure therapy. In the future, this may help reduce distress during treatment for anxiety or trauma-related disorders.

黃仲豪（2024）。探討大鼠右美托嘧啶誘導麻醉下的抑制型逃避學習記憶消除及其神經機制。〔未出版之碩士論文〕。國立成功大學心理學研究所碩士論文https://hdl.handle.net/11296/79wgme
鄭茜馨（2023）。大鼠在右美托嘧啶誘導麻醉下學習味覺嫌惡制約與其神經機制。〔未出版之碩士論文〕。國立成功大學心理學研究所碩士論文 https://hdl.handle.net/11296/mstfbc
蕭翔允（2017）。大鼠在右美托嘧啶誘導麻醉下學習抑制型逃避學習作業與其神經機制。〔未出版之碩士論文〕。國立成功大學心理學研究所碩士論文 https://hdl.handle.net/11296/a5kggq
Alkire, M. T., & Gorski, L. A. (2004). Relative amnesic potency of five inhalational anesthetics follows the Meyer-Overton rule. Anesthesiology, 101(2), 417-429. https://doi.org/10.1097/00000542-200408000-00023
Anderson, J. R. (2000). Learning and memory: An integrated approach. John Wiley & Sons Inc.
Arakawa, H., & Iguchi, Y. (2018). Ethological and multi-behavioral analysis of learning and memory performance in laboratory rodent models. Neuroscience Research, 135, 1-12.
Azevedo, M., Martinho, R., Oliveira, A., Correia-de-Sá, P., & Moreira-Rodrigues, M. (2024). Molecular pathways underlying sympathetic autonomic overshooting leading to fear and traumatic memories: looking for alternative therapeutic options for post-traumatic stress disorder [Review]. Frontiers in Molecular Neuroscience, 16. https://doi.org/10.3389/fnmol.2023.1332348
Baldi, E., & Bucherelli, C. (2015). Brain sites involved in fear memory reconsolidation and extinction of rodents. Neuroscience and Biobehavioral Reviews, 53, 160-190. https://doi.org/10.1016/j.neubiorev.2015.04.003
Basu, A., Yang, J. H., Yu, A., Glaeser-Khan, S., Rondeau, J. A., Feng, J., Krystal, J. H., Li, Y., & Kaye, A. P. (2024). Frontal Norepinephrine Represents a Threat Prediction Error Under Uncertainty. Biological Psychiatry, 96(4), 256-267. https://doi.org/10.1016/j.biopsych.2024.01.025
Bayer, H., Hassell, J. E., Jr., Oleksiak, C. R., Garcia, G. M., Vaughan, H. L., Juliano, V. A. L., & Maren, S. (2024). Pharmacological stimulation of infralimbic cortex after fear conditioning facilitates subsequent fear extinction. bioRxiv. https://doi.org/10.1101/2024.03.23.586410
Becker, D. E., & Reed, K. L. (2012). Local anesthetics: review of pharmacological considerations. Anesthesia Progress, 59(2), 90-102. https://doi.org/10.2344/0003-3006-59.2.90
Berridge, C. W., & Waterhouse, B. D. (2003). The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Research: Brain Research Reviews, 42(1), 33-84. https://doi.org/10.1016/s0165-0173(03)00143-7
Bierwirth, P., & Stockhorst, U. (2022). Role of noradrenergic arousal for fear extinction processes in rodents and humans. Neurobiology of Learning and Memory, 194, 107660. https://doi.org/10.1016/j.nlm.2022.107660
Bonhomme, V., Staquet, C., Montupil, J., Defresne, A., Kirsch, M., Martial, C., Vanhaudenhuyse, A., Chatelle, C., Larroque, S. K., Raimondo, F., Demertzi, A., Bodart, O., Laureys, S., & Gosseries, O. (2019). General Anesthesia: A Probe to Explore Consciousness. Frontiers in Systems Neuroscience, 13, 36. https://doi.org/10.3389/fnsys.2019.00036
Bouton, M. E. (2004). Context and behavioral processes in extinction. Learning and Memory, 11(5), 485-494. https://doi.org/10.1101/lm.78804
Brown, E. N., Lydic, R., & Schiff, N. D. (2010). General anesthesia, sleep, and coma. New England Journal of Medicine, 363(27), 2638-2650. https://doi.org/10.1056/NEJMra0808281
Burgos-Robles, A., Vidal-Gonzalez, I., Santini, E., & Quirk, G. J. (2007). Consolidation of fear extinction requires NMDA receptor-dependent bursting in the ventromedial prefrontal cortex. Neuron, 53(6), 871-880. https://doi.org/10.1016/j.neuron.2007.02.021
Carollo, D. S., Nossaman, B. D., & Ramadhyani, U. (2008). Dexmedetomidine: a review of clinical applications. Current Opinion in Anesthesiology, 21(4), 457-461. https://doi.org/10.1097/ACO.0b013e328305e3ef
Chen, S., Li, B., Hu, Y., Zhang, Y., Dai, W., Zhang, X., Zhou, Y., & Su, D. (2024). Common functional mechanisms underlying dynamic brain network changes across five general anesthetics: A rat fMRI study. CNS Neuroscience & Therapeutics, 30(7), e14866. https://doi.org/10.1111/cns.14866
Chung, H. S. (2014). Awareness and recall during general anesthesia. Korean Journal of Anesthesiology, 66(5), 339-345. https://doi.org/10.4097/kjae.2014.66.5.339
Cobcroft, M. D., & Forsdick, C. (1993). Awareness under Anaesthesia: The Patients’ Point of View. Anaesthesia and Intensive Care, 21(6), 837-843. https://doi.org/10.1177/0310057X9302100616
Correa-Sales, C., Rabin, B. C., & Maze, M. (1992). A hypnotic response to dexmedetomidine, an alpha 2 agonist, is mediated in the locus coeruleus in rats. Anesthesiology, 76(6), 948-952. https://doi.org/10.1097/00000542-199206000-00013
Cruz, E., López, A. V., & Porter, J. T. (2014). Spontaneous Recovery of Fear Reverses Extinction-Induced Excitability of Infralimbic Neurons. PloS One, 9(8), e103596. https://doi.org/10.1371/journal.pone.0103596
Curzon, P., Rustay, N. R., & Browman, K. E. (2009). Cued and Contextual Fear Conditioning for Rodents. In J. J. Buccafusco (Ed.), Methods of Behavior Analysis in Neuroscience (2nd ed.). CRC Press/Taylor & Francis.
de Kleine, R. A., Rothbaum, B. O., & van Minnen, A. (2013). Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review. Eur J Psychotraumatol, 4. https://doi.org/10.3402/ejpt.v4i0.21626
Deeprose, C., & Andrade, J. (2006). Is priming during anesthesia unconscious? Consciousness and Cognition, 15(1), 1-23. https://doi.org/https://doi.org/10.1016/j.concog.2005.05.003
Deeprose, C., Andrade, J., Varma, S., & Edwards, N. (2004). Unconscious learning during surgery with propofol anaesthesia. British Journal of Anaesthesia, 92(2), 171-177. https://doi.org/https://doi.org/10.1093/bja/aeh054
Diekelmann, S., & Born, J. (2010). The memory function of sleep. Nature Reviews: Neuroscience, 11(2), 114-126. https://doi.org/10.1038/nrn2762
Do-Monte, F. H., Manzano-Nieves, G., Quiñones-Laracuente, K., Ramos-Medina, L., & Quirk, G. J. (2015). Revisiting the role of infralimbic cortex in fear extinction with optogenetics. Journal of Neuroscience, 35(8), 3607-3615. https://doi.org/10.1523/jneurosci.3137-14.2015
Do-Monte, F. H. M., Kincheski, G. C., Pavesi, E., Sordi, R., Assreuy, J., & Carobrez, A. P. (2010). Role of beta-adrenergic receptors in the ventromedial prefrontal cortex during contextual fear extinction in rats. Neurobiology of Learning and Memory, 94(3), 318-328. https://doi.org/https://doi.org/10.1016/j.nlm.2010.07.004
Domjan, M. P. (2014). The principles of learning and behavior. Cengage Learning.
Doze, V. A., Chen, B. X., & Maze, M. (1989). Dexmedetomidine produces a hypnotic-anesthetic action in rats via activation of central alpha-2 adrenoceptors. Anesthesiology, 71(1), 75-79. https://doi.org/10.1097/00000542-198907000-00014
Duss, S. B., Oggier, S., Reber, T. P., & Henke, K. (2011). Formation of semantic associations between subliminally presented face-word pairs. Consciousness and Cognition, 20(3), 928-935. https://doi.org/https://doi.org/10.1016/j.concog.2011.03.018
Duss, S. B., Reber, T. P., Hänggi, J., Schwab, S., Wiest, R., Müri, R. M., Brugger, P., Gutbrod, K., & Henke, K. (2014). Unconscious relational encoding depends on hippocampus. Brain, 137(Pt 12), 3355-3370. https://doi.org/10.1093/brain/awu270
Edeline, J.-M., & Neuenschwander-El Massioui, N. (1988). Retention of CS-US association learned under ketamine anesthesia. Brain Research, 457(2), 274-280. https://doi.org/https://doi.org/10.1016/0006-8993(88)90696-8
Eiden, L. E. (2013). Neuropeptide-catecholamine interactions in stress. Advances in Pharmacology, 68, 399-404. https://doi.org/10.1016/b978-0-12-411512-5.00018-x
Fanselow, M. S. (1980). Conditioned and unconditional components of post-shock freezing. Pavlovian Journal of Biological Science, 15(4), 177-182. https://doi.org/10.1007/bf03001163
Fiorenza, N., Rosa, J., Izquierdo, I., & Myskiw, J. (2012). Modulation of the extinction of two different fear-motivated tasks in three distinct brain areas. Behavioural Brain Research, 232, 210-216. https://doi.org/10.1016/j.bbr.2012.04.015
Franklin, S., Baars, B., Ramamurthy, U., & Ventura, M. (2005). The Role of Consciousness in Memory [Electronic Article]. Brains, Minds & Media, 1, Article bmm150. Retrieved 01/01, from https://www.brains-minds-media.org/archive/150
Franks, N. P. (2008). General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal. Nature Reviews Neuroscience, 9(5), 370-386. https://doi.org/10.1038/nrn2372
Franks, N. P., & Zecharia, A. Y. (2011). Sleep and general anesthesia. Canadian Journal of Anaesthesia, 58(2), 139-148. https://doi.org/10.1007/s12630-010-9420-3
Ginsburg, S., & Jablonka, E. (2010). The evolution of associative learning: A factor in the Cambrian explosion. Journal of Theoretical Biology, 266(1), 11-20. https://doi.org/10.1016/j.jtbi.2010.06.017
Giustino, T. F., & Maren, S. (2018). Noradrenergic Modulation of Fear Conditioning and Extinction. Frontiers in Behavioral Neuroscience, 12, 43. https://doi.org/10.3389/fnbeh.2018.00043
Gold, P. E., & Van Buskirk, R. B. (1975). Facilitation of time-dependent memory processes with posttrial epinephrine injections. Behavioral Biology, 13(2), 145-153. https://doi.org/10.1016/s0091-6773(75)91784-8
Guldenmund, P., Vanhaudenhuyse, A., Sanders, R. D., Sleigh, J., Bruno, M. A., Demertzi, A., Bahri, M. A., Jaquet, O., Sanfilippo, J., Baquero, K., Boly, M., Brichant, J. F., Laureys, S., & Bonhomme, V. (2017). Brain functional connectivity differentiates dexmedetomidine from propofol and natural sleep. British Journal of Anaesthesia, 119(4), 674-684. https://doi.org/https://doi.org/10.1093/bja/aex257
Haaker, J., Maren, S., Andreatta, M., Merz, C. J., Richter, J., Richter, S. H., Meir Drexler, S., Lange, M. D., Jüngling, K., Nees, F., Seidenbecher, T., Fullana, M. A., Wotjak, C. T., & Lonsdorf, T. B. (2019). Making translation work: Harmonizing cross-species methodology in the behavioural neuroscience of Pavlovian fear conditioning. Neuroscience and Biobehavioral Reviews, 107, 329-345. https://doi.org/https://doi.org/10.1016/j.neubiorev.2019.09.020
Hamilton, C., Ma, Y., & Zhang, N. (2017). Global reduction of information exchange during anesthetic-induced unconsciousness. Brain Structure & Function, 222(7), 3205-3216. https://doi.org/10.1007/s00429-017-1396-0
Herry, C., Ciocchi, S., Senn, V., Demmou, L., Müller, C., & Lüthi, A. (2008). Switching on and off fear by distinct neuronal circuits. Nature, 454(7204), 600-606. https://doi.org/10.1038/nature07166
Hikind, N., & Maroun, M. (2008). Microinfusion of the D1 receptor antagonist, SCH23390 into the IL but not the BLA impairs consolidation of extinction of auditory fear conditioning. Neurobiology of Learning and Memory, 90(1), 217-222. https://doi.org/10.1016/j.nlm.2008.03.003
Huupponen, E., Maksimow, A., Lapinlampi, P., Särkelä, M., Saastamoinen, A., Snapir, A., Scheinin, H., Scheinin, M., Meriläinen, P., Himanen, S. L., & Jääskeläinen, S. (2008). Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep. Acta Anaesthesiologica Scandinavica, 52(2), 289-294. https://doi.org/10.1111/j.1399-6576.2007.01537.x
Introini-Collison, I. B., & McGaugh, J. L. (1986). Epinephrine modulates long-term retention of an aversively motivated discrimination. Behavioral and Neural Biology, 45(3), 358-365. https://doi.org/10.1016/s0163-1047(86)80024-3
Iselin-Chaves, I. A., Willems, S. J., Jermann, F. C., Forster, A., Adam, S. R., & Van der Linden, M. (2005). Investigation of implicit memory during isoflurane anesthesia for elective surgery using the process dissociation procedure. Anesthesiology, 103(5), 925-933. https://doi.org/10.1097/00000542-200511000-00005
Jami, S. A., Wilkinson, B. J., Guglietta, R., Hartel, N., Babiec, W. E., Graham, N. A., Coba, M. P., & O'Dell, T. J. (2023). Functional and phosphoproteomic analysis of β-adrenergic receptor signaling at excitatory synapses in the CA1 region of the ventral hippocampus. Scientific Reports, 13(1), 7493. https://doi.org/10.1038/s41598-023-34401-7
Kim, E. J., Horovitz, O., Pellman, B. A., Tan, L. M., Li, Q., Richter-Levin, G., & Kim, J. J. (2013). Dorsal periaqueductal gray-amygdala pathway conveys both innate and learned fear responses in rats. Proceedings of the National Academy of Sciences of the United States of America, 110(36), 14795-14800. https://doi.org/10.1073/pnas.1310845110
Knowles, K. A., & Tolin, D. F. (2022). Mechanisms of Action in Exposure Therapy. Current psychiatry reports, 24(12), 861-869. https://doi.org/10.1007/s11920-022-01391-8
LaLumiere, R. T., Niehoff, K. E., & Kalivas, P. W. (2010). The infralimbic cortex regulates the consolidation of extinction after cocaine self-administration. Learning and Memory, 17(4), 168-175. https://doi.org/10.1101/lm.1576810
Laurent, V., & Westbrook, R. F. (2009). Inactivation of the infralimbic but not the prelimbic cortex impairs consolidation and retrieval of fear extinction. Learning and Memory, 16(9), 520-529. https://doi.org/10.1101/lm.1474609
Laureys, S. (2005). The neural correlate of (un)awareness: lessons from the vegetative state. Trends in Cognitive Sciences, 9(12), 556-559. https://doi.org/https://doi.org/10.1016/j.tics.2005.10.010
Li, Y., Zhi, W., Qi, B., Wang, L., & Hu, X. (2023). Update on neurobiological mechanisms of fear: illuminating the direction of mechanism exploration and treatment development of trauma and fear-related disorders. Frontiers in Behavioral Neuroscience, 17, 1216524. https://doi.org/10.3389/fnbeh.2023.1216524
Liang, Z., Lan, Z., Wang, Y., Bai, Y., He, J., Wang, J., & Li, X. (2023). The EEG complexity, information integration and brain network changes in minimally conscious state patients during general anesthesia. Journal of neural engineering, 20(6). https://doi.org/10.1088/1741-2552/ad12dc
Lingawi, N. W., Westbrook, R. F., & Laurent, V. (2017). Extinction and Latent Inhibition Involve a Similar Form of Inhibitory Learning that is Stored in and Retrieved from the Infralimbic Cortex. Cerebral Cortex, 27(12), 5547-5556. https://doi.org/10.1093/cercor/bhw322
Luppi, A. I., Craig, M. M., Pappas, I., Finoia, P., Williams, G. B., Allanson, J., Pickard, J. D., Owen, A. M., Naci, L., Menon, D. K., & Stamatakis, E. A. (2019). Consciousness-specific dynamic interactions of brain integration and functional diversity. Nature Communications, 10(1), 4616. https://doi.org/10.1038/s41467-019-12658-9
Marek, R., & Sah, P. (2018). Neural Circuits Mediating Fear Learning and Extinction. Adv Neurobiol, 21, 35-48. https://doi.org/10.1007/978-3-319-94593-4_2
Maren, S., & Holmes, A. (2016). Stress and Fear Extinction. Neuropsychopharmacology, 41(1), 58-79. https://doi.org/10.1038/npp.2015.180
McDonald, A. J., Mascagni, F., & Guo, L. (1996). Projections of the medial and lateral prefrontal cortices to the amygdala: a Phaseolus vulgaris leucoagglutinin study in the rat. Neuroscience, 71(1), 55-75. https://doi.org/10.1016/0306-4522(95)00417-3
McGaugh, J. L. (2015). Consolidating memories. Annual Review of Psychology, 66, 1-24. https://doi.org/10.1146/annurev-psych-010814-014954
Meamar, M., Rashidy-Pour, A., Rahmani, M., Vafaei, A. A., & Raise-Abdullahi, P. (2023). Glucocorticoid- β-adrenoceptors interactions in the infralimbic cortex in acquisition and consolidation of auditory fear memory extinction in rats. Pharmacology Biochemistry and Behavior, 225, 173560. https://doi.org/https://doi.org/10.1016/j.pbb.2023.173560
Mechias, M.-L., Etkin, A., & Kalisch, R. (2010). A meta-analysis of instructed fear studies: Implications for conscious appraisal of threat. Neuroimage, 49(2), 1760-1768. https://doi.org/https://doi.org/10.1016/j.neuroimage.2009.09.040
Mednick, S., Nakayama, K., & Stickgold, R. (2003). Sleep-dependent learning: a nap is as good as a night. Nature Neuroscience, 6(7), 697-698. https://doi.org/10.1038/nn1078
Milad, M. R., & Quirk, G. J. (2002). Neurons in medial prefrontal cortex signal memory for fear extinction. Nature, 420(6911), 70-74. https://doi.org/10.1038/nature01138
Miserendino, M. J., Sananes, C. B., Melia, K. R., & Davis, M. (1990). Blocking of acquisition but not expression of conditioned fear-potentiated startle by NMDA antagonists in the amygdala. Nature, 345(6277), 716-718. https://doi.org/10.1038/345716a0
Miyashita, T., & Williams, C. L. (2006). Epinephrine administration increases neural impulses propagated along the vagus nerve: Role of peripheral β-adrenergic receptors. Neurobiology of Learning and Memory, 85(2), 116-124. https://doi.org/https://doi.org/10.1016/j.nlm.2005.08.013
Moerman, N., Bonke, B., & Oosting, J. (1993). Awareness and recall during general anesthesia. Facts and feelings. Anesthesiology, 79(3), 454-464. https://doi.org/10.1097/00000542-199309000-00007
Morand-Ferron, J. (2017). Why learn? The adaptive value of associative learning in wild populations. Current Opinion in Behavioral Sciences, 16, 73-79. https://doi.org/https://doi.org/10.1016/j.cobeha.2017.03.008
Mueller, D., & Cahill, S. P. (2010). Noradrenergic modulation of extinction learning and exposure therapy. Behavioural Brain Research, 208(1), 1-11. https://doi.org/10.1016/j.bbr.2009.11.025
Mueller, D., Porter, J. T., & Quirk, G. J. (2008). Noradrenergic signaling in infralimbic cortex increases cell excitability and strengthens memory for fear extinction. Journal of Neuroscience, 28(2), 369-375. https://doi.org/10.1523/jneurosci.3248-07.2008
Myers, K. M., & Davis, M. (2002). Behavioral and neural analysis of extinction. Neuron, 36(4), 567-584. https://doi.org/10.1016/s0896-6273(02)01064-4
Nacif-Coelho, C., Correa-Sales, C., Chang, L. L., & Maze, M. (1994). Perturbation of ion channel conductance alters the hypnotic response to the alpha 2-adrenergic agonist dexmedetomidine in the locus coeruleus of the rat. Anesthesiology, 81(6), 1527-1534. https://doi.org/10.1097/00000542-199412000-00029
Nelson, Laura E., Lu, J., Guo, T., Saper, Clifford B., Franks, Nicholas P., & Maze, M. (2003). The α2-Adrenoceptor Agonist Dexmedetomidine Converges on an Endogenous Sleep-promoting Pathway to Exert Its Sedative Effects. Anesthesiology, 98(2), 428-436. https://doi.org/10.1097/00000542-200302000-00024
Nelson, L. E., You, T., Maze, M., & Franks, N. P. (2001). Evidence that the mechanism of hypnotic action in dexmedetomidine and muscimol-induced anesthesia converges on the endogenous sleep pathway. Anesthesiology, 95, A1368.
Oyarzún, J. P., Càmara, E., Kouider, S., Fuentemilla, L., & de Diego-Balaguer, R. (2019). Implicit but not explicit extinction to threat-conditioned stimulus prevents spontaneous recovery of threat-potentiated startle responses in humans. Brain and behavior, 9(1), e01157. https://doi.org/10.1002/brb3.1157
Pang, R., Turndorf, H., & Quartermain, D. (1996). Pavlovian fear conditioning in mice anesthetized with halothane. Physiology and Behavior, 59(4), 873-875. https://doi.org/https://doi.org/10.1016/0031-9384(95)02137-X
Pavlov, P. I. (2010). Conditioned reflexes: An investigation of the physiological activity of the cerebral cortex. Ann Neurosci, 17(3), 136-141. https://doi.org/10.5214/ans.0972-7531.1017309
Paxinos, G., & Watson, C. (2006). The rat brain in stereotaxic coordinates: hard cover edition. Elsevier.
Perouansky, M., Rau, V., Ford, T., Oh, S. I., Perkins, M., Eger, E. I., 2nd, & Pearce, R. A. (2010). Slowing of the hippocampal θ rhythm correlates with anesthetic-induced amnesia. Anesthesiology, 113(6), 1299-1309. https://doi.org/10.1097/ALN.0b013e3181f90ccc
Quirk, G. J., Likhtik, E., Pelletier, J. G., & Paré, D. (2003). Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons. Journal of Neuroscience, 23(25), 8800-8807. https://doi.org/10.1523/jneurosci.23-25-08800.2003
Raskin, M., & Monfils, M. H. (2023). Reconsolidation and Fear Extinction: An Update. Current Topics in Behavioral Neurosciences, 64, 307-333. https://doi.org/10.1007/7854_2023_438
Reber, T. P., & Henke, K. (2011). Rapid formation and flexible expression of memories of subliminal word pairs. Frontiers in Psychology, 2, 343. https://doi.org/10.3389/fpsyg.2011.00343
Rumpel, S., LeDoux, J., Zador, A., & Malinow, R. (2005). Postsynaptic receptor trafficking underlying a form of associative learning. Science, 308(5718), 83-88. https://doi.org/10.1126/science.1103944
Samuel, N., Taub, A. H., Paz, R., & Raz, A. (2018). Implicit aversive memory under anaesthesia in animal models: a narrative review. British Journal of Anaesthesia, 121(1), 219-232. https://doi.org/https://doi.org/10.1016/j.bja.2018.05.046
Sanders, R. D., Tononi, G., Laureys, S., & Sleigh, J. W. (2012). Unresponsiveness ≠ unconsciousness. Anesthesiology, 116(4), 946-959. https://doi.org/10.1097/ALN.0b013e318249d0a7
Schafe, G. E., Nader, K., Blair, H. T., & LeDoux, J. E. (2001). Memory consolidation of Pavlovian fear conditioning: a cellular and molecular perspective. Trends in Neurosciences, 24(9), 540-546. https://doi.org/10.1016/s0166-2236(00)01969-x
Senn, V., Wolff, S. B., Herry, C., Grenier, F., Ehrlich, I., Gründemann, J., Fadok, J. P., Müller, C., Letzkus, J. J., & Lüthi, A. (2014). Long-range connectivity defines behavioral specificity of amygdala neurons. Neuron, 81(2), 428-437. https://doi.org/10.1016/j.neuron.2013.11.006
Sierra-Mercado, D., Padilla-Coreano, N., & Quirk, G. J. (2011). Dissociable Roles of Prelimbic and Infralimbic Cortices, Ventral Hippocampus, and Basolateral Amygdala in the Expression and Extinction of Conditioned Fear. Neuropsychopharmacology, 36(2), 529-538. https://doi.org/10.1038/npp.2010.184
Sleigh, J., Warnaby, C., & Tracey, I. (2018). General anaesthesia as fragmentation of selfhood: insights from electroencephalography and neuroimaging. British Journal of Anaesthesia, 121(1), 233-240. https://doi.org/10.1016/j.bja.2017.12.038
Smith, C. N., & Squire, L. R. (2018). Awareness of what is learned as a characteristic of hippocampus-dependent memory. Proceedings of the National Academy of Sciences, 115(47), 11947-11952. https://doi.org/doi:10.1073/pnas.1814843115
Smith, G., D'Cruz, J. R., Rondeau, B., & Goldman, J. (2018). General anesthesia for surgeons. https://www.ncbi.nlm.nih.gov/books/NBK493199/
Sonner, J. M., Cascio, M., Xing, Y., Fanselow, M. S., Kralic, J. E., Morrow, A. L., Korpi, E. R., Hardy, S., Sloat, B., Eger, E. I., 2nd, & Homanics, G. E. (2005). Alpha 1 subunit-containing GABA type A receptors in forebrain contribute to the effect of inhaled anesthetics on conditioned fear. Molecular Pharmacology, 68(1), 61-68. https://doi.org/10.1124/mol.104.009936
Sotres-Bayon, F., & Quirk, G. J. (2010). Prefrontal control of fear: more than just extinction. Current Opinion in Neurobiology, 20(2), 231-235. https://doi.org/10.1016/j.conb.2010.02.005
Squire, L. R., & Dede, A. J. (2015). Conscious and unconscious memory systems. Cold Spring Harbor Perspectives in Biology, 7(3), a021667. https://doi.org/10.1101/cshperspect.a021667
Stern, C. A., Gazarini, L., Vanvossen, A. C., Hames, M. S., & Bertoglio, L. J. (2013). Activity in prelimbic cortex subserves fear memory reconsolidation over time. Learn Mem, 21(1), 14-20. https://doi.org/10.1101/lm.032631.113
Szeleszczuk, Ł., & Frączkowski, D. (2022). Propranolol versus Other Selected Drugs in the Treatment of Various Types of Anxiety or Stress, with Particular Reference to Stage Fright and Post-Traumatic Stress Disorder. International Journal of Molecular Sciences, 23(17). https://doi.org/10.3390/ijms231710099
Team, R. (2019). RStudio: Integrated Development for R. (RStudio, Inc., Boston, MA). http://www.rstudio.com/.
Team, R. C. (2020). R: A language and environment for statistical computing. (R Foundation for Statistical Computing, Vienna, Austria.). https://www.R-project.org/.
Torras-Garcia, M., Portell-Cortés, I., & Morgado-Bernal, I. (1997). Long-Term Memory Modulation by Posttraining Epinephrine in Rats: Differential Effects Depending on the Basic Learning Capacity. Behavioral Neuroscience, 111, 301-308. https://doi.org/10.1037/0735-7044.111.2.301
Tovote, P., Fadok, J. P., & Lüthi, A. (2015). Neuronal circuits for fear and anxiety. Nature Reviews Neuroscience, 16(6), 317-331. https://doi.org/10.1038/nrn3945
Tucker, M. A., Hirota, Y., Wamsley, E. J., Lau, H., Chaklader, A., & Fishbein, W. (2006). A daytime nap containing solely non-REM sleep enhances declarative but not procedural memory. Neurobiology of Learning and Memory, 86(2), 241-247. https://doi.org/10.1016/j.nlm.2006.03.005
Vargas, L. d. S., Lima, K. R., & Mello-Carpes, P. B. (2021). Infralimbic and prelimbic prefrontal cortex activation is necessary to the enhancement of aversive memory extinction promoted by reactivation. Brain Research, 1770, 147630. https://doi.org/https://doi.org/10.1016/j.brainres.2021.147630
Vervliet, B., Craske, M. G., & Hermans, D. (2013). Fear extinction and relapse: state of the art. Annual Review of Clinical Psychology, 9, 215-248. https://doi.org/10.1146/annurev-clinpsy-050212-185542
Vidal-Gonzalez, I., Vidal-Gonzalez, B., Rauch, S. L., & Quirk, G. J. (2006). Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear. Learning and Memory, 13(6), 728-733. https://doi.org/10.1101/lm.306106
Walker, A. G., Sheffler, D. J., Lewis, A. S., Dickerson, J. W., Foster, D. J., Senter, R. K., Moehle, M. S., Lv, X., Stansley, B. J., Xiang, Z., Rook, J. M., Emmitte, K. A.,Lindsley, C. W., & Conn, P. J. (2017). Co-Activation of Metabotropic Glutamate Receptor 3 and Beta-Adrenergic Receptors Modulates Cyclic-AMP and Long-Term Potentiation, and Disrupts Memory Reconsolidation. Neuropsychopharmacology, 42(13), 2553-2566. https://doi.org/10.1038/npp.2017.136
Walker, R. A., Wright, K. M., Jhou, T. C., & McDannald, M. A. (2020). The ventrolateral periaqueductal grey updates fear via positive prediction error. European Journal of Neuroscience, 51(3), 866-880. https://doi.org/10.1111/ejn.14536
Watanabe, M., Uematsu, A., & Johansen, J. P. (2021). Enhanced synchronization between prelimbic and infralimbic cortices during fear extinction learning. Molecular Brain, 14(1), 175. https://doi.org/10.1186/s13041-021-00884-6
Watanabe, M., Uematsu, A., & Johansen, J. P. (2025). Bidirectional emotional regulation through prefrontal innervation of the locus coeruleus. Molecular Psychiatry. https://doi.org/10.1038/s41380-025-02944-y
Weinberger, N. M., Gold, P. E., & Sternberg, D. B. (1984). Epinephrine enables Pavlovian fear conditioning under anesthesia. Science, 223(4636), 605-607. https://doi.org/10.1126/science.6695173
Williams, C. L., & McGaugh, J. L. (1993). Reversible lesions of the nucleus of the solitary tract attenuate the memory-modulating effects of posttraining epinephrine. Behavioral Neuroscience, 107(6), 955-962.
Wong, D. L., Siddall, B., & Wang, W. (1995). Hormonal control of rat adrenal phenylethanolamine N-methyltransferase. Enzyme activity, the final critical pathway. Neuropsychopharmacology, 13(3), 223-234. https://doi.org/10.1016/0893-133x(95)00066-m
Xing, B., Li, Y. C., & Gao, W. J. (2016). Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex. Brain Research, 1641(Pt B), 217-233. https://doi.org/10.1016/j.brainres.2016.01.005
Yu, S. Y., Wu, D. C., Liu, L., Ge, Y., & Wang, Y. T. (2008). Role of AMPA receptor trafficking in NMDA receptor-dependent synaptic plasticity in the rat lateral amygdala. Journal of Neurochemistry, 106(2), 889-899. https://doi.org/10.1111/j.1471-4159.2008.05461.x
Zhou, H. C., Sun, Y. Y., Cai, W., He, X. T., Yi, F., Li, B. M., & Zhang, X. H. (2013). Activation of β2-adrenoceptor enhances synaptic potentiation and behavioral memory via cAMP-PKA signaling in the medial prefrontal cortex of rats. Learning and Memory, 20(5), 274-284. https://doi.org/10.1101/lm.030411.113