うつ病のメカニズムと抗うつ作用に関する近年の動物研究の動向
DOI:
https://doi.org/10.51094/jxiv.2493キーワード:
うつ病、 モノアミン、 動物モデル、 炎症、 幻覚剤、 神経回路抄録
うつ病は生涯にわたり発症し得る有病率の高い精神疾患であるが、その病態生理は依然として十分には解明されていない。これまでの基礎研究および臨床研究の蓄積により、モノアミン神経伝達の異常がうつ病の発症に関与することが示唆され、この知見に基づいて、選択的セロトニン再取り込み阻害薬やセロトニン・ノルアドレナリン再取り込み阻害薬などの抗うつ薬が開発され、広く臨床に用いられてきた。しかし、これら従来型抗うつ薬は効果発現までに数週間を要し、長期的な服用が必要であるにもかかわらず、約3割の患者では十分な治療効果が得られないことが知られている。加えて、一部の患者においては自殺念慮の増加など重篤な副作用も報告されており、有効性および安全性の両面から、新規治療戦略の確立が喫緊の課題となっている。近年、ケタミンや幻覚薬に代表される薬物が即効性かつ持続的な抗うつ効果を示すことが明らかとなり、従来のモノアミン仮説のみでは説明し得ない新たな病態メカニズムに注目が集まっている。これらの知見は、グルタミン酸神経伝達、シナプス可塑性、さらには免疫—脳相互作用など、多様な生物学的機構が抗うつ作用に不可欠であることを示唆すると同時に、長年支持されてきた神経伝達物質異常仮説を再検討する契機ともなっている。さらに、脳回路レベルでの機序解明を含む基礎研究の進展は、うつ病の新たな治療戦略の構築に大きく寄与しつつある。本総説では、抗うつ薬開発の歴史的背景と近年の新規作用機序に関する再評価を概観するとともに、主要なうつ病動物モデルの特性とモデル研究の意義を整理し、基礎研究から臨床応用へと接続する橋渡し研究の最新動向について概説する。
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引用文献
Abela, A. R., Browne, C. J., Sargin, D., Prevot, T. D., Ji, X. D., Li, Z., Lambe, E. K., & Fletcher, P. J. (2020). Median raphe serotonin neurons promote anxiety like behavior via inputs to the dorsal hippocampus. Neuropharmacology, 168, 107985. https://doi.org/10.1016/j.neuropharm.2020.107985
Acher, F. C. (2011). Metabotropic Glutamate Receptors. Tocris Bioscience Scientific Review Series, 26, 1-20.
Aizawa, H., Amo, R., & Okamoto, H. (2011). Phylogeny and ontogeny of the habenular structure. Frontiers in Neuroscience, 5, 138. https://doi.org/10.3389/fnins.2011.00138
Aldosary, F., Norris, S., Tremblay, P., James, J. S., Ritchie, J. C., & Blier, P. (2022). Differential Potency of Venlafaxine, Paroxetine, and Atomoxetine to Inhibit Serotonin and Norepinephrine Reuptake in Patients With Major Depressive Disorder. International Journal of Neuropsychopharmacology, 25(4), 283–292. https://doi.org/10.1093/ijnp/pyab086
Amat, J., Baratta, M. V., Paul, E., Bland, S. T., Watkins, L. R., & Maier, S. F. (2005). Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nature Neuroscience, 8(3), 365-71. https://doi.org/10.1038/nn1399
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed., pp. 160–179). American Psychiatric Publishing.
Anttila, S. A., & Leinonen, E. V. (2001). A review of the pharmacological and clinical profile of mirtazapine. CNS drug reviews, 7(3), 249–264. https://doi.org/10.1111/j.1527-3458.2001.tb00198.x
Arosio, B., Guerini, F. R., Oude Voshaar, R. C., & Aprahamian, I. (2021). Blood brain derived neurotrophic factor (BDNF) and major depression: Do we have a translational perspective? Frontiers in Behavioral Neuroscience, 15, 626906. https://doi.org/10.3389/fnbeh.2021.626906
Austelle, C. W., O’Leary, G. H., Thompson, S., Gruber, E., Kahn, A., Manett, A. J., Short, B., & Badran, B. W. (2022). A Comprehensive Review of Vagus Nerve Stimulation for Depression. Neuromodulation, 25(3), 309–315. https://doi.org/10.1111/ner.13528
Autry, A. E., Adachi, M., Nosyreva, E., Na, E. S., Los, M. F., Cheng, P. F., Kavalali, E. T., & Monteggia, L. M. (2011). NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature, 475(7354), 91–95. https://doi.org/10.1038/nature10130
Bajbouj, M., Merkl, A., Schlaepfer, T. E., Frick, C., Zobel, A., Maier, W., O'Keane, V., Corcoran, C., Adolfsson, R., Trimble, M., Rau, H., Hoff, H. J., Padberg, F., Müller-Siecheneder, F., Audenaert, K., van den Abbeele, D., Matthews, K., Christmas, D., Eljamel, S., & Heuser, I. (2010). Two-year outcome of vagus nerve stimulation in treatment-resistant depression. Journal of Clinical Psychopharmacology, 30(3), 273–281. https://doi.org/10.1097/JCP.0b013e3181db8831
Banks, W. A., Gray, A. M., Erickson, M. A., Salameh, T. S., Damodarasamy, M., Sheibani, N., Meabon, J. S., Wing, E. E., Morofuji, Y., Cook, D. G., & Reed, M. J. (2015). Lipopolysaccharide-induced blood-brain barrier disruption: Roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit. Journal of Neuroinflammation, 12, 223. https://doi.org/10.1186/s12974-015-0434-1
Bauer, M., Tharmanathan, P., Volz, H. P., Moeller, H. J., & Freemantle, N. (2009). The effect of venlafaxine compared with other antidepressants and placebo in the treatment of major depression: a meta-analysis. European Archives of Psychiatry and Clinical Neuroscience, 259(3), 172–185. https://doi.org/10.1007/s00406-008-0849-0
Belujon, P., & Grace, A. A. (2017). Dopamine system dysregulation in major depressive disorders. International Journal of Neuropsychopharmacology, 20(12), 1036–1046. https://doi.org/10.1093/ijnp/pyx056
Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2000). Antidepressant effects of ketamine in depressed patients. Biological Psychiatry, 47(4), 351-354. https://doi.org/10.1016/S0006-3223(99)00230-9
Berthoux, C., Marin, P., Felder-Schmittbuhl, M.-P., Bécamel, C., & Marin, P. (2018). Sustained activation of postsynaptic 5 HT₂A receptors gates plasticity at prefrontal cortex synapses. Cerebral Cortex, 29(4), 1659–1669. https://doi.org/10.1093/cercor/bhy064
Beurel, E., Song, L., & Jope, R. S. (2011). Inhibition of glycogen synthase kinase-3 is necessary for the rapid antidepressant effect of ketamine in mice. Molecular Psychiatry, 16(11), 1068–1070. https://doi.org/10.1038/mp.2011.47
Birkinshaw, H., Friedrich, C., Cole, P., Eccleston, C., Serfaty, M., Stewart, G., White, S., Moore, A., Phillippo, D., & Pincus, T. (2024). Antidepressants for pain management in adults with chronic pain: A network meta-analysis. Health Technology Assessment, 28(62), 1–155. https://doi.org/10.3310/MKRT2948
Blier, P., & de Montigny, C. (1994). Current advances and trends in the treatment of depression. Trends in Pharmacological Sciences, 15(7), 220–226. https://doi.org/10.1016/0165-6147(94)90315-8
Bobkova, N. V., Chuvakova, L. N., Kovalev, V. I., Zhdanova, D. Y., Chaplygina, A. V., Rezvykh, A. P., & Evgen'ev, M. B. (2025). A Mouse Model of Sporadic Alzheimer's Disease with Elements of Major Depression. Molecular neurobiology, 62(2), 1337–1358. https://doi.org/10.1007/s12035-024-04346-7
Boulton, A. A., Baker, G. B., & Greenshaw, A. J. (Eds.) (2018). Hallucinogens, PCP, and Ketamine. In Psychopharmacology (3rd ed., pp.500-515). Humana Press.
Brodkin, J., Bradbury, M., Busse, C., Warren, N., Bristow, L. J., & Varney, M. A. (2002). Reduced stress-induced hyperthermia in mGluR5 knockout mice. European Journal of Neuroscience, 16(12), 2301–2307. https://doi.org/10.1046/j.1460-9568.2002.02294.x
Bymaster, F. P., Lee, T. C., Knadler, M. P., Detke, M. J., & Iyengar, S. (2005). The dual transporter inhibitor duloxetine: A review of its preclinical pharmacology, pharmacokinetic profile, and clinical results in depression. Current Pharmaceutical Design, 11(12), 1475–1493. https://doi.org/10.2174/1381612053764805
Cahn, C. (2006). Roland Kuhn, 1912–2005. Neuropsychopharmacology, 31(5), 1096. https://doi.org/10.1038/sj.npp.1301026
Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M., Erritzoe, D., Kaelen, M., Bloomfield, M., Rickard, J. A., Forbes, B., Feilding, A., Taylor, D., Pilling, S., Curran, V. H., & Nutt, D. J. (2016). Psilocybin with psychological support for treatment-resistant depression: An open-label feasibility study. Lancet Psychiatry, 3(7), 619–627. https://doi.org/10.1016/S2215-0366(16)30065-7
Carhart-Harris, R. L., Bolstridge, M., Day, C. M. J., Rucker, J., Watts, R., Erritzoe, D. E., Kaelen, M., Giribaldi, B., Bloomfield, M., Pilling, S., Rickard, J. A., Forbes, B., Feilding, A., Taylor, D., Curran, H. V., & Nutt, D. J. (2018). Psilocybin with psychological support for treatment-resistant depression: Six-month follow-up. Psychopharmacology, 235(2), 399–408. https://doi.org/10.1007/s00213-017-4771-x.
Caldecott-Hazard, S., Mazziotta, J., & Phelps, M. (1988). Cerebral correlates of depressed behavior in rats, visualized using 14C-2-deoxyglucose autoradiography. The Journal of neuroscience : the official journal of the Society for Neuroscience, 8(6), 1951–1961. https://doi.org/10.1523/JNEUROSCI.08-06-01951.1988
Carlsson, A. (2018, July 1). Arvid Carlsson. Sahlgrenska Academy. Retrieved December 6, 2024, from https://web.archive.org/web/20180701030548/https://sahlgrenska.gu.se/english/research/researchers/arvid-carlsson
Carlsson, A., Corrodi, H., Fuxe, K., & Hökfelt, T. (1969). Effect of antidepressant drugs on the depletion of intraneuronal brain 5-hydroxytryptamine stores caused by 4-methyl-alpha-ethyl-meta-tyramine. European Journal of Pharmacology, 5(4), 357–366. https://doi.org/10.1016/0014-2999(69)90113-7
Carregosa, D., Loncarevic-Vasiljkovic, N., Feliciano, R., Moura-Louro, D., Mendes, C. S., & Dos Santos, C. N. (2024). Locomotor and gait changes in the LPS model of neuroinflammation are correlated with inflammatory cytokines in blood and brain. Journal of Inflammation, 21(1), 39. https://doi.org/10.1186/s12950-024-00412-y
CenterWatch. (2025, October 2). Investigation of the antidepressant effects of (2R,6R)-HNK, an enhancer of synaptic glutamate release, in treatment-resistant depression (Clinical trial NCT06511908). https://www.centerwatch.com/clinical-trials/listings/NCT06511908/investigation-of-the-antidepressant-effects-of-2r6r-hnk-an-enhancer-of-synaptic-glutamate-release-in-treatment-resistant-depression
Chaki, S., & Watanabe, M. (2023). mGlu2/3 receptor antagonists for depression: overview of underlying mechanisms and clinical development. European Archives of Psychiatry and Clinical Neuroscience, 273(7), 1451–1462. https://doi.org/10.1007/s00406-023-01561-6
Chekroud, A. M., Zotti, R. J., Shehzad, Z., Gueorguieva, R., Johnson, M. K., Trivedi, M. H., Cannon, T. D., Krystal, J. H., & Corlett, P. R. (2016). Cross-trial prediction of treatment outcome in depression: a machine learning approach. The Lancet. Psychiatry, 3(3), 243–250. https://doi.org/10.1016/S2215-0366(15)00471-X
Chen, X., Liu, X., Luan, S., Liu, Y., Song, D., Zhang, H., Sun, Y., Wang, T., Liu, X., & Yan, J. (2024). Optogenetic activation of the lateral habenula D1R–ventral tegmental area circuit induces depression-like behavior in mice. European Archives of Psychiatry and Clinical Neuroscience, 274(6), 867–878. https://doi.org/10.1007/s00406-023-01743-2
Chessin, M., Kramer, E. R., & Scott, C. C. (1957). Modifications of the pharmacology of reserpine and serotonin by iproniazid. The Journal of Pharmacology and Experimental Therapeutics, 119(4), 453 460.
Chinta, S. J., & Andersen, J. K. (2005). Dopaminergic neurons. The International Journal of Biochemistry & Cell Biology, 37(5), 942–946. https://doi.org/10.1016/j.biocel.2004.12.011
Christensen, J., Grønborg, T. K., Sørensen, M. J., Schendel, D., Parner, E. T., Pedersen, L. H., & Vestergaard, M. (2013). Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA, 309(16), 1696–1703. https://doi.org/10.1001/jama.2013.2270
Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., Leucht, S., Ruhe, H. G., Turner, E. H., Higgins, J. P. T., Egger, M., Takeshima, N., Hayasaka, Y., Imai, H., Shinohara, K., Tajika, A., Ioannidis, J. P. A., & Geddes, J. R. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. The Lancet, 391(10128), 1357–1366. https://doi.org/10.1016/S0140-6736(17)32802-7
Cohen, J. Y., Amoroso, M. W., & Uchida, N. (2015). Serotonergic neurons signal reward and punishment on multiple timescales. eLife, 4, e06346. https://doi.org/10.7554/eLife.06346
Cole, A. B., Montgomery, K., Bale, T. L., & Thompson, S. M. (2022). What the hippocampus tells the HPA axis: Hippocampal output attenuates acute stress responses via disynaptic inhibition of CRF+ PVN neurons. Neurobiology of Stress, 20, 100473. https://doi.org/10.1016/j.ynstr.2022.100473
Commons, K. G., & Linnros, S. E. (2019). Delayed antidepressant efficacy and the desensitization hypothesis. ACS Chemical Neuroscience, 10(7), 3048–3052. https://doi.org/10.1021/acschemneuro.8b00698
Conway, C. R., Aaronson, S. T., Sackeim, H. A., George, M. S., Zajecka, J., Bunker, M. T., Duffy, W., Stedman, M., Riva Posse, P., Allen, R. M., Quevedo, J., Berger, M., Alva, G., Malik, M. A., Dunner, D. L., Cichowicz, I., Banov, M., Manu, L., Nahas, Z., Macaluso, M., Mickey, B. J., Sheline, Y., Kriedt, C. L., Lee, Y. C., Gordon, C., Shy, O., Tran, Q., Yates, L., & Rush, A. J. (2025 May Jun). Vagus nerve stimulation in treatment resistant depression: A one year, randomized, sham controlled trial. Brain Stimulation, 18(3), 676 689. https://doi.org/10.1016/j.brs.2024.12.1191
Cools, R., Roberts, A. C., & Robbins, T. W. (2008). Serotoninergic regulation of emotional and behavioural control processes. Trends in Cognitive Sciences, 12(1), 31-40. https://doi.org/10.1016/j.tics.2007.10.011
Cording, M., Derry, S., Phillips, T., Moore, R. A., & Wiffen, P. J. (2015). Milnacipran for pain in fibromyalgia in adults. Cochrane Database of Systematic Reviews, 10, CD008244. https://doi.org/10.1002/14651858.CD008244.pub3
Cosci, F., & Chouinard, G. (2019). The monoamine hypothesis of depression revisited: Could it mechanistically novel antidepressant strategies? In J. Quevedo, A. F. Carvalho, & C. A. Zarate (Eds.), Neurobiology of Depression (pp. 63–73). Academic Press. https://doi.org/10.1016/B978-0-12-813333-0.00007-X
Cui, Y., Yang, Y., Ni, Z., Dong, Y., Cai, G., Foncelle, A., Ma, S., Hu, H., & Li, B. (2018). Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression. Nature, 554(7692), 323–327. https://doi.org/10.1038/nature25752
Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2021). Effects of psilocybin-assisted therapy on major depressive disorder: A randomized clinical trial. JAMA Psychiatry, 78(5), 481–489. https://doi.org/10.1001/jamapsychiatry.2020.3285
de Freitas, C. M., Busanello, A., Schaffer, L. F., Peroza, L. R., Krum, B. N., Leal, C. Q., Ceretta, A. P., da Rocha, J. B., & Fachinetto, R. (2016). Behavioral and neurochemical effects induced by reserpine in mice. Psychopharmacology, 233(3), 457–467. https://doi.org/10.1007/s00213-015-4118-4
de Souza, F. S., & Franci, C. R. (2008). GABAergic mediation of stress-induced secretion of corticosterone and oxytocin, but not prolactin, by the hypothalamic paraventricular nucleus. Life Sciences, 83(21 22), 768–774. https://doi.org/10.1016/j.lfs.2008.09.007
Donahue, R. J., Muschamp, J. W., Russo, S. J., Nestler, E. J., & Carlezon, W. A., Jr (2014). Effects of striatal ΔFosB overexpression and ketamine on social defeat stress-induced anhedonia in mice. Biological Psychiatry, 76(7), 550–558. https://doi.org/10.1016/j.biopsych.2013.12.014
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010). A meta-analysis of cytokines in major depression. Biological Psychiatry, 67(5), 446-457. https://doi.org/10.1016/j.biopsych.2009.09.033
Duman, R. S., & Monteggia, L. M. (2006). A neurotrophic model for stress related mood disorders. Biological Psychiatry, 59(12), 1116–1127. https://doi.org/10.1016/j.biopsych.2006.02.013
Duman, R. S., Heninger, G. R., & Nestler, E. J. (1997). A molecular and cellular theory of depression. Archives of General Psychiatry, 54(7), 597–606. https://doi.org/10.1001/archpsyc.1997.01830190015002
Dwyer, J. M., Lepack, A. E., & Duman, R. S. (2012). mTOR activation is required for the antidepressant effects of mGluR₂/₃ blockade. The International Journal of Neuropsychopharmacology, 15(4), 429–434. https://doi.org/10.1017/S1461145711001702
Farina de Almeida, R., Ganzella, M., Machado, D. G., Loureiro, S. O., Leffa, D., Quincozes-Santos, A., Pettenuzzo, L. F., Frescura Duarte, M. M. M., Duarte, T., & Souza, D. O. (2017). Olfactory bulbectomy in mice triggers transient and long-lasting behavioral impairments and biochemical hippocampal disturbances. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 76, 1–11. https://doi.org/10.1016/j.pnpbp.2017.02.003
Feyissa, A. M., Woolverton, W. L., Miguel Hidalgo, J. J., Wang, Z., Kyle, P. B., Hasler, G., Stockmeier, C. A., Iyo, A. H., & Karolewicz, B. (2010). Elevated level of metabotropic glutamate receptor 2/3 in the prefrontal cortex in major depression. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 34(2), 279–283. https://doi.org/10.1016/j.pnpbp.2009.11.018
Fogaça, M. V., & Duman, R. S. (2019). Cortical GABAergic dysfunction in stress and depression: New insights for therapeutic interventions. Frontiers in Cellular Neuroscience, 13, 87. https://doi.org/10.3389/fncel.2019.00087
Fonseca, M. S., Murakami, M., & Mainen, Z. F. (2015). Activation of dorsal raphe serotonergic neurons promotes waiting but is not reinforcing. Current Biology, 25(3), 306–315. https://doi.org/10.1016/j.cub.2014.12.002
Fortin, J. S., Lafleur, M., Parisien, C., & Hétu, S. (2025). The habenula in mood disorders: A systematic review of human studies. Molecular Psychiatry, 2025 Oct;30(10):4948-4970. https://doi.org/10.1038/s41380-025-03105-x
Franco, R., Reyes Resina, I., & Navarro, G. (2021). Dopamine in health and disease: Much more than a neurotransmitter. Biomedicines, 9(2), 109. https://doi.org/10.3390/biomedicines9020109
Freis, E. D. (1954). Mental depression in hypertensive patients treated for long periods with large doses of reserpine. The New England Journal of Medicine, 251(25), 1006–1008. https://doi.org/10.1056/NEJM195412162512504
Fries, G. R., Saldana, V. A., & Finnstein, J. (2023). Molecular pathways of major depressive disorder converge on the synapse. Molecular Psychiatry, 28(1), 284–297. https://doi.org/10.1038/s41380-022-01806-1
Frisbee, J. C., Brooks, S. D., Stanley, S. C., & d'Audiffret, A. C. (2015). An unpredictable chronic mild stress protocol for instigating depressive symptoms, behavioral changes, and negative health outcomes in rodents. Journal of Visualized Experiments, 106, https://doi.org/10.3791/53109
Fritze, S., Spanagel, R., & Noori, H. R. (2017). Adaptive dynamics of the 5-HT systems following chronic administration of selective serotonin reuptake inhibitors: A meta-analysis. Journal of Neurochemistry, 142(5), 747–755. https://doi.org/10.1111/jnc.14114
Gazdag, G., Bitter, I., Ungvari, G. S., & Baran, B. (2009). Convulsive therapy turns 75. British Journal of Psychiatry, 194(5), 387-388. https://doi.org/10.1192/bjp.bp.108.062547
Gao, Z. Y., Yang, P., Huang, Q. J., & Xu, H. Y. (2016). The influence of dizocilpine on the reserpine-induced behavioral and neurobiological changes in rats. Neuroscience Letters, 614, 89–94. https://doi.org/10.1016/j.neulet.2016.01.006
Geyer, M. A., Wilkinson, L. S., Humby, T., & Robbins, T. W. (1993). Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophrenia. Biological Psychiatry, 34(6), 361–372. https://doi.org/10.1016/0006-3223(93)90180-l
Gilles, Y. D., & Polston, E. K. (2017). Effects of social deprivation on social and depressive-like behaviors and the numbers of oxytocin expressing neurons in rats. Behavioural Brain Research, 328, 28–38. https://doi.org/10.1016/j.bbr.2017.03.036
Guo, J., Lin, P., Zhao, X., Zhang, J., Wei, X., Wang, Q., & Wang, C. (2014). Etazolate abrogates the lipopolysaccharide (LPS)-induced downregulation of the cAMP/pCREB/BDNF signaling, neuroinflammatory response, and depressive-like behavior in mice. Neuroscience, 263, 1-14. https://doi.org/10.1016/j.neuroscience.2014.01.008
Glassman, A. H., & Bigger, J. T. Jr. (1981). Cardiovascular effects of therapeutic doses of tricyclic antidepressants: A review. Archives of General Psychiatry, 38(7), 815–820. https://doi.org/10.1001/archpsyc.1981.01780320095011
Gray, N. A., Milak, M. S., DeLorenzo, C., Ogden, R. T., Huang, Y. Y., Mann, J. J., & Parsey, R. V. (2013). Antidepressant treatment reduces serotonin-1A autoreceptor binding in major depressive disorder. Biological Psychiatry, 74(1), 26–31. https://doi.org/10.1016/j.biopsych.2012.11.012
Golden, S. A., Covington, H. E., 3rd, Berton, O., & Russo, S. J. (2011). A standardized protocol for repeated social defeat stress in mice. Nature Protocols, 6(8), 1183–1191. https://doi.org/10.1038/nprot.2011.361
Han, X., Wang, W., Shao, F., & Li, N. (2011). Isolation rearing alters social behaviors and monoamine neurotransmission in the medial prefrontal cortex and nucleus accumbens of adult rats. Brain Research, 1385, 175–181. https://doi.org/10.1016/j.brainres.2011.02.035
Hao, Y., Ge, H., Sun, M., & Gao, Y. (2019). Selecting an appropriate animal model of depression. International Journal of Molecular Sciences, 20(19), 4827. https://doi.org/10.3390/ijms20194827
Hashimoto, K., Sawa, A., & Iyo, M. (2007). Increased levels of glutamate in brains from patients with mood disorders. Biological Psychiatry, 62(11), 1310–1316. https://doi.org/10.1016/j.biopsych.2007.03.017
Hassanein, E. H. M., Althagafy, H. S., Baraka, M. A., Abd alhameed, E. K., & Ibrahim, I. M. (2023). Pharmacological update of mirtazapine: a narrative literature review. Naunyn Schmiedeberg’s Archives of Pharmacology, 397(5), 2603 2619. https://doi.org/10.1007/s00210-023-02818-6
Hatch, A. M., Wiberg, G. S., Zawidzka, Z., Cann, M., Airth, J. M., & Grice, H. C. (1965). Isolation syndrome in the rat. Toxicology and Applied Pharmacology, 7(5), 737–745. https://doi.org/10.1016/0041-008X(65)90132-8
Hayashi, K., Nakao, K., & Nakamura, K. (2015). Appetitive and aversive information coding in the primate dorsal raphé nucleus. The Journal of Neuroscience : the official journal of the Society for Neuroscience, 35(15), 6195–6208. https://doi.org/10.1523/JNEUROSCI.2860-14.2015
Healy, D. (2000). Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression. James Lorimer & Company.
Hellweg, R., Zueger, M., Fink, K., Hörtnagl, H., & Gass, P. (2007). Olfactory bulbectomy in mice leads to increased BDNF levels and decreased serotonin turnover in depression-related brain areas. Neurobiology of Disease, 25(1), 1–7. https://doi.org/10.1016/j.nbd.2006.08.006
Herkenham, M., & Nauta, W. J. H. (1979). Efferent connections of the habenular nuclei in the rat. The Journal of Comparative Neurology, 187(1), 19–47. https://doi.org/10.1002/cne.901870103
Hermes, G., Li, N., Duman, C., & Duman, R. S. (2011). Post-weaning chronic social isolation produces profound behavioral dysregulation with decreases in prefrontal cortex synaptic-associated protein expression in female rats. Physiology & Behavior, 104(2), 354–359. https://doi.org/10.1016/j.physbeh.2010.12.019
Hikosaka, O. (2010). The habenula: from stress evasion to value-based decision-making. Nature Reviews Neuroscience, 11, 503–513. https://doi.org/10.1038/nrn2866
Hu, H., Cui, Y. & Yang, Y. (2020). Circuits and functions of the lateral habenula in health and in disease. Nature Reviews Neuroscience, 21, 277–295. https://doi.org/10.1038/s41583-020-0292-4
Huang, K. W., Ochandarena, N. E., Philson, A. C., Hyun, M., Birnbaum, J. E., Cicconet, M., & Sabatini, B. L. (2019). Molecular and anatomical organization of the dorsal raphe nucleus. eLife, 8, e46464. https://doi.org/10.7554/eLife.46464
Huys, Q., Maia, T. & Frank, M. Computational psychiatry as a bridge from neuroscience to clinical applications. Nature Neuroscience, 19, 404–413 (2016). https://doi.org/10.1038/nn.4238
Inaba, K., Mizuhiki, T., Setogawa, T., Toda, K., Richmond, B. J., & Shidara, M. (2013). Neurons in monkey dorsal raphe nucleus code beginning and progress of step-by-step schedule, reward expectation, and amount of reward outcome in the reward schedule task. The Journal of neuroscience : the official journal of the Society for Neuroscience, 33(8), 3477–3491. https://doi.org/10.1523/JNEUROSCI.4388-12.2013
Ishikawa, H., Kawakami, N., Kessler, R. C., & World Mental Health Japan Survey Collaborators (2016). Lifetime and 12-month prevalence, severity and unmet need for treatment of common mental disorders in Japan: Results from the final dataset of World Mental Health Japan Survey. Epidemiology and Psychiatric Sciences, 25(3), 217–229. https://doi.org/10.1017/S2045796015000566
Jauhar, S., Arnone, D., Baldwin, D. S., Goodwin, G. M., Geddes, J. R., & Young, A. H. (2023). A leaky umbrella has little value: Evidence clearly indicates the serotonin system is implicated in depression. Molecular Psychiatry, 28(9), 3149–3152. https://doi.org/10.1038/s41380-023-02095-y
Jiang, Y., Zou, M., Ren, T., & Wang, Y. (2023). Are mGluR2/3 Inhibitors Potential Compounds for Novel Antidepressants? Cellular and Molecular Neurobiology, 43, 1931–1940. https://doi.org/10.1007/s10571-022-01310-8
Jin, H., Li, M., Jeong, E., Castro Martinez, F., & Zuker, C. S. (2024). A body–brain circuit that regulates body inflammatory responses. Nature, 630(8017), 695–703. https://doi.org/10.1038/s41586-024-07469-y
Joffe, M. E., Santiago, C. I., Oliver, K. H., Maksymetz, J., Harris, N. A., Engers, J. L., Lindsley, C. W., Winder, D. G., & Conn, P. J. (2020). mGlu2 and mGlu3 Negative Allosteric Modulators Divergently Enhance Thalamocortical Transmission and Exert Rapid Antidepressant-like Effects. Neuron, 105(1), 46-59. https://doi.org/10.1016/j.neuron.2019.09.044
Johnson, S. A., Fournier, N. M., & Kalynchuk, L. E. (2006). Effect of different doses of corticosterone on depression-like behavior and HPA axis responses to a novel stressor. Behavioural Brain Research, 168(2), 280–288. https://doi.org/10.1016/j.bbr.2005.11.019
Jones K. (2000). Insulin coma therapy in schizophrenia. Journal of the Royal Society of Medicine, 93(3), 147-149. https://doi.org/10.1177/014107680009300313
Jourdi, H., Hsu, Y. T., Zhou, M., Qin, Q., Bi, X., & Baudry, M. (2009). Positive AMPA receptor modulation rapidly stimulates BDNF release and increases dendritic mRNA translation. The Journal of Neuroscience : the official journal of the Society for Neuroscience, 29(27), 8688–8697. https://doi.org/10.1523/JNEUROSCI.6078-08.2009
Kamp, C. B., Petersen, J. J., Faltermeier, P., Juul, S., Siddiqui, F., Barbateskovic, M., Kristensen, A. T., Moncrieff, J., Horowitz, M. A., Hengartner, M. P., Kirsch, I., Gluud, C., & Jakobsen, J. C. (2024). Beneficial and harmful effects of tricyclic antidepressants for adults with major depressive disorder: A systematic review with meta-analysis and trial sequential analysis. BMJ Mental Health, 27(1), e300730. https://doi.org/10.1136/bmjment-2023-300730
Kavalali, E. T., & Monteggia, L. M. (2025). Synaptic basis of rapid antidepressant action. European archives of psychiatry and clinical neuroscience, 275(6), 1539–1546. https://doi.org/10.1007/s00406-024-01898-6
Kawai, H., Bouchekioua, Y., Nishitani, N., Niitani, K., Izumi, S., Morishita, H., Andoh, C., Nagai, Y., Koda, M., Hagiwara, M., Toda, K., Shirakawa, H., Nagayasu, K., Ohmura, Y., Kondo, M., Kaneda, K., Yoshioka, M., & Kaneko, S. (2022). Median raphe serotonergic neurons projecting to the interpeduncular nucleus control preference and aversion. Nature Communications, 13, 7708. https://doi.org/10.1038/s41467-022-35346-7
Kellner, C. H., Rubinow, D. R., & Post, R. M. (1986). Cerebral ventricular size and cognitive impairment in depression. Journal of Affective Disorders, 10(3), 215–219. https://doi.org/10.1016/0165-0327(86)90007-8
Kielholz, P. (1968). Diagnose und Therapie der Depressionen für den Praktiker (pp. 82–87). Bern, Switzerland: Hans Huber.
King, M. G., & Cairncross, K. D. (1974). Effects of olfactory bulb section on brain noradrenaline, corticosterone and conditioning in the rat. Pharmacology Biochemistry and Behavior, 2(3), 347–353. https://doi.org/10.1016/0091-3057(74)90079-3
Kinlein, S. A., Wilson, C. D., & Karatsoreos, I. N. (2015). Dysregulated hypothalamic–pituitary–adrenal axis function contributes to altered endocrine and neurobehavioral responses to acute stress. Frontiers in Psychiatry, 6, 31. https://doi.org/10.3389/fpsyt.2015.00031
Kline, N.S., & Cooper, T.B. (1980). Monoamine Oxidase Inhibitors as Antidepressants. In: Hoffmeister, F., Stille, G. (eds) Psychotropic Agents. Handbook of Experimental Pharmacology, vol 55 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-67538-6_17
Koike, H., & Chaki, S. (2014). Requirement of AMPA receptor stimulation for the sustained antidepressant activity of ketamine and LY341495 during the forced swim test in rats. Behavioural Brain Research, 271, 111–115. https://doi.org/10.1016/j.bbr.2014.05.065
Koike, H., Fukumoto, K., Iijima, M., & Chaki, S. (2013). Role of BDNF/TrkB signaling in antidepressant like effects of a group II metabotropic glutamate receptor antagonist in animal models of depression. Behavioural Brain Research, 238, 48–52. https://doi.org/10.1016/j.bbr.2012.10.023
Kryst, J., Kawalec, P., Mitoraj, A. M., Pilc, A., Lasoń, W., & Brzostek, T. (2020). Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: A meta-analysis of randomized clinical trials. Pharmacological Reports, 72, 543–562. https://doi.org/10.1007/s43440-020-00097-z
Krystal, J. H., Kavalali, E. T., & Monteggia, L. M. (2024). Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 49(1), 41–50. https://doi.org/10.1038/s41386-023-01629-w
Lanquillon, S., Krieg, J. C., Bening-Abu-Shach, U., & Vedder, H. (2000). Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology, 22(4), 370-379. https://doi.org/10.1016/S0893-133X(99)00134-7
Lecca, S., Pelosi, A., Tchenio, A., Moutkine, I., Luján, R., Hervé, D., & Mameli, M. (2016). Rescue of GABA₍B₎ and GIRK function in the lateral habenula by protein phosphatase 2A inhibition ameliorates depression-like phenotypes in mice. Nature Medicine, 22(3), 254–261. https://doi.org/10.1038/nm.4037
Lepack, A. E., Fuchikami, M., Dwyer, J. M., Banasr, M., & Duman, R. S. (2015). BDNF release is required for the behavioral actions of ketamine. International Journal of Neuropsychopharmacology, 18(1). https://doi.org/10.1093/ijnp/pyu033
Li, L., & Vlisides, P. E. (2016). Ketamine: 50 years of modulating the mind. Frontiers in Human Neuroscience, 10, 612. https://doi.org/10.3389/fnhum.2016.00612
Li, R., Zhao, D., Qu, R., Fu, Q., & Ma, S. (2015). The effects of apigenin on lipopolysaccharide-induced depressive-like behavior in mice. Neuroscience Letters, 594, 17-22. https://doi.org/10.1016/j.neulet.2015.03.040
Liu, R. J., Fuchikami, M., Dwyer, J. M., Lepack, A. E., Duman, R. S., & Aghajanian, G. K. (2013). GSK-3 inhibition potentiates the synaptogenic and antidepressant-like effects of subthreshold doses of ketamine. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 38(11), 2268–2277. https://doi.org/10.1038/npp.2013.128
Li, Y., Zhong, W., Wang, D., Feng, Q., Liu, Z., Zhou, J., Jia, C., Hu, F., Zeng, J., Guo, Q., Fu, L., & Luo, M. (2016). Serotonin neurons in the dorsal raphe nucleus encode reward signals. Nature Communications, 7, 10503. https://doi.org/10.1038/ncomms10503
Li, W., Ali, T., He, K., Liu, Z., Shah, F. A., Ren, Q., Liu, Y., Jiang, A., & Li, S. (2021). Ibrutinib alleviates LPS-induced neuroinflammation and synaptic defects in a mouse model of depression. Brain, Behavior, and Immunity, 92, 10-24. https://doi.org/10.1016/j.bbi.2020.11.008
Liu, B., Cao, Y., Wang, J., & Dong, J. (2020). Excitatory transmission from ventral pallidum to lateral habenula mediates depression. The World Journal of Biological Psychiatry, 21(8), 627–633. https://doi.org/10.1080/15622975.2020.1725117
Liu, R. J., Fuchikami, M., Dwyer, J. M., Lepack, A. E., Duman, R. S., & Aghajanian, G. K. (2013). GSK-3 inhibition potentiates the synaptogenic and antidepressant-like effects of subthreshold doses of ketamine. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 38(11), 2268–2277. https://doi.org/10.1038/npp.2013.128
López-Giménez, J. F., & González-Maeso, J. (2018). Hallucinogens and serotonin 5-HT2A receptor-mediated signaling pathways. Current Topics in Behavioral Neurosciences, 36, 45–73. https://doi.org/10.1007/7854_2017_478
López-Muñoz, F., & Alamo, C. (2009). Monoaminergic neurotransmission: the history of the discovery of antidepressants f rom 1950s until today. Current Pharmaceutical Design, 15(14), 1563-86. https://doi.org/10.2174/138161209788168001
Lottem, E., Banerjee, D., Vertechi, P., Sarra, D., Lohuis, M. O., & Mainen, Z. F. (2018). Activation of serotonin neurons promotes active persistence in a probabilistic foraging task. Nature Communications, 9(1), 1000. https://doi.org/10.1038/s41467-018-03438-y
Lowry, C. A., Hale, M. W., Evans, A. K., Heerkens, J., Staub, D. R., Gasser, P. J., & Shekhar, A. (2008). Serotonergic systems, anxiety, and affective disorder: focus on the dorsomedial part of the dorsal raphe nucleus. Annals of the New York Academy of Sciences, 1148, 86-94. https://doi.org/10.1196/annals.1410.004
Lumsden, E. W., Troppoli, T. A., Myers, S. J., Zanos, P., Aracava, Y., Kehr, J., Lovett, J., Kim, S., Wang, F. H., Schmidt, S., Jenne, C. E., Yuan, P., Morris, P. J., Thomas, C. J., Zarate, C. A. Jr., Moaddel, R., Traynelis, S. F., Pereira, E. F. R., Thompson, S. M., Albuquerque, E. X., & Gould, T. D. (2019). Antidepressant-relevant concentrations of the ketamine metabolite (2R,6R)-hydroxynorketamine do not block NMDA receptor function. Proceedings of the National Academy of Sciences of the United States of America, 116(11), 5160–5169. https://doi.org/10.1073/pnas.1816071116
Luo, M., Zhou, J., & Liu, Z. (2015). Reward processing by the dorsal raphe nucleus: 5-HT and beyond. Learning & Memory, 22(9), 452–460. https://doi.org/10.1101/lm.037317.114
Luo, Y., Cao, Z., Wang, D., Wu, L., Li, Y., Sun, W., & Zhu, Y. (2014). Dynamic study of the hippocampal volume by structural MRI in a rat model of depression. Neurological Sciences, 35, 1777–1783. https://doi.org/10.1007/s10072-014-1837-y
Lv, H., Zhao, Y., Chen, J., Wang, D., & Chen, H. (2019). Vagus nerve stimulation for depression: A systematic review. Frontiers in Psychology, 10, 64. https://doi.org/10.3389/fpsyg.2019.00064
Ma, X. C., Dang, Y. H., Jia, M., Ma, R., Wang, F., Wu, J., Gao, C. G., & Hashimoto, K. (2013). Long-lasting antidepressant action of ketamine, but not glycogen synthase kinase-3 inhibitor SB216763, in the chronic mild stress model of mice. PLoS ONE, 8(2), e56053. https://doi.org/10.1371/journal.pone.0056053
Machado, M., & Einarson, T. R. (2010). Comparison of SSRIs and SNRIs in major depressive disorder: A meta-analysis of head-to-head randomized clinical trials. Journal of Clinical Pharmacy & Therapeutics, 35(2), 177–188. https://doi.org/10.1111/j.1365-2710.2009.01050.x
Madsen, C. A., Navarro, M. L., Elfving, B., Kessing, L. V., Castrén, E., Mikkelsen, J. D., & Knudsen, G. M. (2024). The effect of antidepressant treatment on blood BDNF levels in depressed patients: A review and methodological recommendations for assessment of BDNF in blood. European Neuropsychopharmacology, 87, 35–55. https://doi.org/10.1016/j.euroneuro.2024.06.008
Mahfouz, A., Lelieveldt, B. P. F., Grefhorst, A., van Weert, L. T. C. M., Mol, I. M., Sips, H. C. M., van den Heuvel, J. K., Datson, N. A., Visser, J. A., Reinders, M. J. T., & Meijer, O. C. (2016). Genome-wide coexpression of steroid receptors in the mouse brain: Identifying signaling pathways and functionally coordinated regions. Proceedings of the National Academy of Sciences, 113(10), 2738–2743. https://doi.org/10.1073/pnas.1520376113
Mahlich, J., Tsukazawa, S., & Wiegand, F. (2018). Estimating prevalence and healthcare utilization for treatment-resistant depression in Japan: A retrospective claims database study. Drugs—Real World Outcomes, 5(1), 35–43. https://doi.org/10.1007/s40801-017-0126-5
Maier, S. F., & Watkins, L. R. (2005). Stressor controllability and learned helplessness: the roles of the dorsal raphe nucleus, serotonin, and corticotropin-releasing factor. Neuroscience Biobehavioral Review, 29(4-5), 829-841. https://doi.org/10.1016/j.neubiorev.2005.03.021
Mao, L. M., Mathur, N., Mahmood, T., Rajan, S., Chu, X. P., & Wang, J. Q. (2022). Phosphorylation and regulation of group II metabotropic glutamate receptors (mGlu2/3) in neurons. Frontiers in Cell and Developmental Biology, 10, 1022544. https://doi.org/10.3389/fcell.2022.1022544
Martin, A. L., & Brown, R. E. (2010). The lonely mouse: verification of a separation-induced model of depression in female mice. Behavioural Brain Research, 207(1), 196–207. https://doi.org/10.1016/j.bbr.2009.10.006
Matsushima, Y., Eguchi, F., Kikukawa, T., & Matsuda, T. (2009). Historical overview of psychoactive mushrooms. Inflammation & Regeneration, 29(1), 47–58. https://doi.org/10.2492/inflammregen.29.47
松下 正明・昼田 源四郎. (1999). 精神医療の歴史. 中山書店.
Matveychuk, D., Thomas, R. K., Swainson, J., Khullar, A., MacKay, M. A., Baker, G. B., & Dursun, S. M. (2020). Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers. Therapeutic Advances in Psychopharmacology, 10, https://doi.org/10.1177/2045125320916657
Meyer, J. S., Farrar, A. M., Biezonski, D., & Yates, J. R. (2022). Psychopharmacology: Drugs, the brain, and behavior (4th ed.). Sinauer Associates (Oxford University Press).
Meyer, J. S., & Quenzer, L. F. (2018). Psychopharmacology: Drugs, the brain, and behavior (3rd ed.). Oxford University Press.
Miller, O. H., Yang, L., Wang, C. C., Hargroder, E. A., Zhang, Y., Delpire, E., & Hall, B. J. (2014). GluN2B-containing NMDA receptors regulate depression-like behavior and are critical for the rapid antidepressant actions of ketamine. eLife, 3, e03581. https://doi.org/10.7554/eLife.03581
Miyazaki, K. W., Miyazaki, K., Tanaka, K. F., Yamanaka, A., Takahashi, A., Tabuchi, S., & Doya, K. (2014). Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards. Current Biology, 24(17), 2033–2040. https://doi.org/10.1016/j.cub.2014.07.041
Moghaddam, B., Bolinao, M. L., Stein-Behrens, B., & Sapolsky, R. (1994). Glucocorticoids mediate the stress-induced extracellular accumulation of glutamate. Brain Research, 655(1–2), 251–254. https://doi.org/10.1016/0006-8993(94)91622-5
Molloy, B. B. (1999). Inductee details. The National Inventors Hall of Fame. Retrieved December 6, 2024, from https://www.invent.org/inductees/bryan-b-molloy
Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2023). The serotonin theory of depression: A systematic umbrella review of the evidence. Molecular Psychiatry, 28(9), 3243–3256. https://doi.org/10.1038/s41380-022-01661-0
Morales-Medina, J. C., Iannitti, T., Freeman, A., & Caldwell, H. K. (2017). The olfactory bulbectomized rat as a model of depression: The hippocampal pathway. Behavioural Brain Research, 317, 562–575. https://doi.org/10.1016/j.bbr.2016.09.029
Moriguchi, S., Yamada, M., Takano, H., Nagashima, T., Takahata, K., Yokokawa, K., Ito, T., Ishii, T., Kimura, Y., Zhang, M.-R., Mimura, M., & Suhara, T. (2016). Norepinephrine transporter in major depressive disorder: A PET study. American Journal of Psychiatry, 174(1), 36–41. https://doi.org/10.1176/appi.ajp.2016.15101334
MSD Manuals. (n.d.). Depression: Treatment. MSD Manuals. Retrieved November 5, 2025, from https://www.merckmanuals.com/home/mental-health-issues/mood-disorders/depression-treatment
Muir, J., Lin, S., Aarrestad, I.K., Daniels, H.R., Ma, J., Tian, L., Olson, D.E., & Kim, C.K. (2024). Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states. Science, 386, 802–810. https://doi.org/10.1126/science.adl0666
Naert, G., Maurice, T., Tapia-Arancibia, L., & Givalois, L. (2007). Neuroactive steroids modulate HPA axis activity and cerebral brain-derived neurotrophic factor (BDNF) protein levels in adult male rats. Psychoneuroendocrinology, 32(8-10), 1062–1078. https://doi.org/10.1016/j.psyneuen.2007.09.002
Nakamura, K., Matsumoto, M., & Hikosaka, O. (2008). Reward-dependent modulation of neuronal activity in the primate dorsal raphe nucleus. The Journal of neuroscience : the official journal of the Society for Neuroscience, 28(20), 5331–5343. https://doi.org/10.1523/JNEUROSCI.0021-08.2008
Nestler, E. J., & Russo, S. J. (2024). Neurobiological basis of stress resilience. Neuron, 112(12), 1911–1929. https://doi.org/10.1016/j.neuron.2024.05.001
Nibuya, M., Morinobu, S., & Duman, R. S. (1995). Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. The Journal of Neuroscience : the official journal of the Society for Neuroscience, 15(11), 7539–7547. https://doi.org/10.1523/JNEUROSCI.15-11-07539.1995
野村 総一郎. (2008). うつ病の真実. 日本評論社
Nowak, G., Pomierny-Chamioło, L., Siwek, A., Niedzielska, E., Pomierny, B., Pałucha-Poniewiera, A., & Pilc, A. (2014). Prolonged administration of antidepressant drugs leads to increased binding of [3H]MPEP to mGlu5 receptors. Neuropharmacology, 84, 46–51. https://doi.org/10.1016/j.neuropharm.2014.04.016
岡村 仁. (2011). うつ病のメカニズム. バイオメカニズム学会誌, 35(1), 3–8.
奥沢 康仁. (2002). きのこを薬と副食にしたかかわりの歴史. 日本菌学会会報, 43, 105-117.
大坪 天平. (2022). 抗うつ薬を使いこなす. 女性心身医学, 27(2), 154–158.
Overmier, J. B., & Seligman, M. E. P. (1967). Effects of inescapable shock upon subsequent escape and avoidance learning. Journal of Comparative and Physiological Psychology, 63(1), 28–33. https://doi.org/10.1037/h0024166
Patted, P. G., Masareddy, R. S., Patil, A. S., Kanabargi, R. R., & Bhat, C. T. (2024). Omega-3 fatty acids: A comprehensive scientific review of their sources, functions and health benefits. Future Journal of Pharmaceutical Sciences, 10, 94. https://doi.org/10.1186/s43094-024-00667-5
Park, B. K., Kim, Y. R., Kim, Y. H., Yang, C., Seo, C. S., Jung, I. C., Jang, I. S., Kim, S. H., & Lee, M. Y. (2018). Antidepressant like effects of Gyejibokryeong hwan in a mouse model of reserpine induced depression. Biomedical Research International, 2018, 5845491. https://doi.org/10.1155/2018/5845491
Parker, V., & Morinan, A. (1986). The socially-isolated rat as a model for anxiety. Neuropharmacology, 25(6), 663–664. https://doi.org/10.1016/0028-3908(86)90224-8
Pertovaara, A. (2013). The noradrenergic pain regulation system: A potential target for pain therapy. European Journal of Pharmacology, 716(1–3), 2–7. https://doi.org/10.1016/j.ejphar.2013.01.067
Pham, T. H., Defaix, C., Xu, X., Deng, S. X., Fabresse, N., Alvarez, J. C., Landry, D. W., Brachman, R. A., Denny, C. A., & Gardier, A. M. (2018). Common Neurotransmission Recruited in (R,S)-Ketamine and (2R,6R)-Hydroxynorketamine-Induced Sustained Antidepressant-like Effects. Biological Psychiatry, 84(1), e3–e6. https://doi.org/10.1016/j.biopsych.2017.10.020
Phillips, J. L., Norris, S., Talbot, J., Birmingham, M., Hatchard, T., Ortiz, A., Owoeye, O., Batten, L. A., & Blier, P. (2019). Single, repeated, and maintenance ketamine infusions for treatment-resistant depression: A randomized controlled trial. American Journal of Psychiatry, 176(5), 401–409. https://doi.org/10.1176/appi.ajp.2018.18070834
Piirsalu, M., Taalberg, E., Lilleväli, K., Tian, L., Zilmer, M., & Vasar, E. (2020). Treatment with lipopolysaccharide induces distinct changes in metabolite profile and body weight in 129Sv and Bl6 mouse strains. Frontiers in Pharmacology, 11, 371. https://doi.org/10.3389/fphar.2020.00371
Pilc, A., Chaki, S., Nowak, G., & Witkin, J. M. (2008). Mood disorders: Regulation by metabotropic glutamate receptors. Biochemical Pharmacology, 75(5), 997–1006. https://doi.org/10.1016/j.bcp.2007.09.021
Planchez, B., Surget, A., & Belzung, C. (2019). Animal models of major depression: drawbacks and challenges. Journal of Neural Transmission, 126(11), 1383–1408. https://doi.org/10.1007/s00702-019-02084-y
Pogorelov, V. M., Rodriguiz, R. M., Roth, B. L., & Wetsel, W. C. (2023). The G protein biased serotonin 5-HT2A receptor agonist lisuride exerts anti-depressant drug-like activities in mice. Frontiers in Molecular Biosciences, 10, 1233743. https://doi.org/10.3389/fmolb.2023.1233743
Polter, A. M., & Li, X. (2010). 5-HT1A receptor-regulated signal transduction pathways in brain. Cellular Signalling, 22(10), 1406–1412. https://doi.org/10.1016/j.cellsig.2010.03.019
Potter, L. E., Zanos, P., & Gould, T. D. (2020). Antidepressant Effects and Mechanisms of Group II mGlu Receptor-Specific Negative Allosteric Modulators. Neuron, 105(1), 1-3. https://doi.org/10.1016/j.neuron.2019.12.011
Primeaux, S. D., & Holmes, P. V. (2000). Olfactory bulbectomy increases met-enkephalin- and neuropeptide-Y-like immunoreactivity in rat limbic structures. Pharmacology Biochemistry and Behavior, 67(2), 331–337. https://doi.org/10.1016/S0091-3057(00)00358-0
Raison, C. L., Capuron, L., & Miller, A. H. (2006). Cytokines sing the blues: Inflammation and the pathogenesis of depression. Trends in Immunology, 27(1), 24–31. https://doi.org/10.1016/j.it.2005.11.006
Raja, S. M., Guptill, J. T., Mack, M., Peterson, M., Byard, S., Twieg, R., Jordan, L., Rich, N., Castledine, R., Bourne, S., Wilmshurst, M., Oxendine, S., Avula, S. G. C., Zuleta, H., Quigley, P., Lawson, S., McQuaker, S. J., Ahmadkhaniha, R., Appelbaum, L. G., Kowalski, K., Barksdale, C. T., Gufford, B. T., Awan, A., Sancho, A. R., Moore, M. C., Berrada, K., Cogan, G. B., DeLaRosa, J., Radcliffe, J., Pao, M., Kennedy, M., Lawrence, Q., Goldfeder, L., Amanfo, L., Zanos, P., Gilbert, J. R., Morris, P. J., Moaddel, R., Gould, T. D., Zarate, C. A. Jr., & Thomas, C. J. (2024). A Phase 1 assessment of the safety, tolerability, pharmacokinetics and pharmacodynamics of (2R,6R)-hydroxynorketamine in healthy volunteers. Clinical Pharmacology & Therapeutics, 116(5), 1314–1324. https://doi.org/10.1002/cpt.3391
Ramesh, V., Venkatesan, V., Chellathai, D., & Silamban, S. (2021). Association of serum biomarker levels and BDNF gene polymorphism with response to selective serotonin reuptake inhibitors in Indian patients with major depressive disorder. Neuropsychobiology, 80(3), 201–213. https://doi.org/10.1159/000507371
Richelson, E. (2001). Pharmacology of antidepressants. Mayo Clinic Proceedings, 76(5), 511–527. https://doi.org/10.4065/76.5.511
Riedel, G., Platt, B., & Micheau, J. (2003). Glutamate receptor function in learning and memory. Behavioural Brain Research, 140(1–2), 1–47. https://doi.org/10.1016/S0166-4328(02)00272-3
Rivero, G., Gabilondo, A. M., García Sevilla, J. A., La Harpe, R., Callado, L. F., & Meana, J. J. (2014). Increased α2 and β1 adrenoceptor densities in postmortem brain of subjects with depression: Differential effect of antidepressant treatment. Journal of Affective Disorders, 167, 343 350. https://doi.org/10.1016/j.jad.2014.06.016
Rodoshi, Z. N., Shibu, S., Omer, O., Tallal, H., Gondal, M. Z. D., Shahid, Z., Azam, A., & Abbas, N. (2025). Comparative efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in the management of post-stroke depression: A systematic review of randomized controlled trials. Cureus, 17(5), e84784. https://doi.org/10.7759/cureus.84784
Rush, A. J., & Siefert, S. E. (2009). Clinical issues in considering vagus nerve stimulation for treatment-resistant depression. Experimental Neurology, 219(1), 36–43. https://doi.org/10.1016/j.expneurol.2009.04.015
Rush, A. J., George, M. S., Sackeim, H. A., Marangell, L. B., Husain, M. M., Giller, C., Nahas, Z., Haines, S., Simpson, R. K., & Goodman, R. (2000). Vagus nerve stimulation (VNS) for treatment resistant depressions: A multicenter study. Biological Psychiatry, 47(4), 276 286. https://doi.org/10.1016/S0006-3223(99)00304-2
Salazar, A., Gonzalez-Rivera, B. L., Redus, L., Parrott, J. M., & O'Connor, J. C. (2012). Indoleamine 2,3-dioxygenase mediates anhedonia and anxiety-like behaviors caused by peripheral lipopolysaccharide immune challenge. Hormones and Behavior, 62(3), 202-209. https://doi.org/10.1016/j.yhbeh.2012.03.010
Sandler, M. (1990). Monoamine Oxidase Inhibitors in Depression: History and Mythology. Journal of Psychopharmacology, 4(3), 136-139. https://doi.org/10.1177/026988119000400307
坂本 将俊. (2017). 抗うつ剤の種類・特徴とその限界. ファルマシア, 53(7), 663-667.
Sakel, M. J. (1956) The classical Sakel shock treatment: a reappraisal. In F. Marti-Ibanez et al. (eds.) The great physiodynamic therapies in psychiatry: an historical reappraisal. New York: 13-75.
Sarchiapone, M., Carli, V., Camardese, G., Cuomo, C., Di Giuda, D., Calcagni, M. L., Focacci, C., & De Risio, S. (2006). Dopamine transporter binding in depressed patients with anhedonia. Psychiatry Research, 147(2-3), 243–248. https://doi.org/10.1016/j.pscychresns.2006.03.001
Savić Vujović, K., Jotić, A., Medić, B., Srebro, D., Vujović, A., Žujović, J., Opanković, A., & Vučković, S. (2023). Ketamine, an Old-New Drug: Uses and Abuses. Pharmaceuticals, 17(1), 16. https://doi.org/10.3390/ph17010016
Seo, J. S., Zhong, P., Liu, A., Yan, Z., & Wang, W. (2018). Elevation of p11 in lateral habenula mediates depression-like behavior. Molecular Psychiatry, 23(5), 1113–1119. https://doi.org/10.1038/mp.2017.96
Scott, A. I. (1999). New classes of antidepressant drugs. Advances in Psychiatric Treatment, 5(2), 104 111. https://doi.org/10.1192/apt.5.2.104
Sekssaoui, M., Bockaert, J., Marin, P., Berthoux, C., Gaven, F., Cannich, A., & Chameau, P. (2024). Antidepressant-like effects of psychedelics in a chronic despair mouse model: Is the 5-HT2A receptor the unique player? Neuropsychopharmacology, 49, 747–756. https://doi.org/10.1038/s41386-024-01794-6
Seligman, M. E. P. (1972). Learned helplessness. Annual Review of Medicine, 23, 407–412. https://doi.org/10.1146/annurev.me.23.020172.002203
Seligman, M. E., & Maier, S. F. (1967). Failure to escape traumatic shock. Journal of Experimental Psychology, 74(1), 1–9. https://doi.org/10.1037/h0024514
Selikoff, I. J., Robitzek, E. H., & Ornstein, G. G. (1952). TREATMENT OF PULMONARY TUBERCULOSIS WITH HYDRAZIDE DERIVATIVES OF ISONICOTINIC ACID. JAMA, 150(10), 973–980. https://doi.org/10.1001/jama.1952.03680100015006
Sheline Y. I. (2011). Depression and the hippocampus: cause or effect?. Biological Psychiatry, 70(4), 308–309. https://doi.org/10.1016/j.biopsych.2011.06.006
Shen W. W. (1999). A history of antipsychotic drug development. Comprehensive Psychiatry, 40(6), 407–414. https://doi.org/10.1016/s0010-440x(99)90082-2
Shen, Q., Lal, R., Luellen, B. A., Earnheart, J. C., Andrews, A. M., & Luscher, B. (2010). γ-Aminobutyric acid-type A receptor deficits cause hypothalamic-pituitary-adrenal axis hyperactivity and antidepressant drug sensitivity reminiscent of melancholic forms of depression. Biological Psychiatry, 68(6), 512–520. https://doi.org/10.1016/j.biopsych.2010.04.024
Shirayama, Y., & Hashimoto, K. (2018). Lack of antidepressant effects of (2R,6R)-hydroxynorketamine in a rat learned helplessness model: Comparison with (R)-ketamine. International Journal of Neuropsychopharmacology, 21(1), 84–88. https://doi.org/10.1093/ijnp/pyx108
Shoji, H., Maeda, Y., & Miyakawa, T. (2024). Chronic corticosterone exposure causes anxiety- and depression-related behaviors with altered gut microbial and brain metabolomic profiles in adult male C57BL/6J mice. Molecular Brain, 17(1), 79. https://doi.org/10.1186/s13041-024-01146-x
Singh, A., Bousman, C., Ng, C., Byron, K., & Berk, M. (2013). Psychomotor depressive symptoms may differentially respond to venlafaxine. International Clinical Psychopharmacology, 28. https://doi.org/10.1097/YIC.0b013e32835f1b9f
Smith, R. S. (1991). The macrophage theory of depression. Medical Hypotheses, 35(4), 298-306. https://doi.org/10.1016/0306-9877(91)90272-z
Smith, K. S., & Rudolph, U. (2012). Anxiety and depression: Mouse genetics and pharmacological approaches to the role of GABAA receptor subtypes. Neuropharmacology, 62(1), 54–62. https://doi.org/10.1016/j.neuropharm.2011.07.026
Smith, S. M., & Vale, W. W. (2006). The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues in Clinical Neuroscience, 8(4), 383–395. https://doi.org/10.31887/DCNS.2006.8.4/ssmith
Song, C., & Leonard, B. E. (2005). The olfactory bulbectomised rat as a model of depression. Neuroscience and Biobehavioral Reviews, 29(4-5), 627–647. https://doi.org/10.1016/j.neubiorev.2005.03.010
Stahl, S. M. (2021). Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Cambridge University Press. https://doi.org/10.1017/9781108975292
Stone, M., Laughren, T., Jones, M. L., Levenson, M., Holland, P. C., Hughes, A., Hammad, T. A., Temple, R., & Rochester, G. (2009). Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ, 339, b2880. https://doi.org/10.1136/bmj.b2880
Sturm, M., Becker, A., Schroeder, A., Bilkei-Gorzo, A., & Zimmer, A. (2015). Effect of chronic corticosterone application on depression-like behavior in C57BL/6N and C57BL/6J mice. Genes, Brain and Behavior. https://doi.org/10.1111/gbb.12208
Takaba, R., Ibi, D., Yoshida, K., Hosomi, E., Kawase, R., Kitagawa, H., Goto, H., Achiwa, M., Mizutani, K., Maeda, K., González-Maeso, J., Kitagaki, S., & Hiramatsu, M. (2024). Ethopharmacological evaluation of antidepressant-like effect of serotonergic psychedelics in C57BL/6J male mice. Naunyn-Schmiedeberg's Archives of Pharmacology, 397(5), 3019-3035. https://doi.org/10.1007/s00210-023-02778-x
Tang, X. H., Zhang, G. F., Xu, N., Duan, G. F., Jia, M., Liu, R., Zhou, Z. Q., & Yang, J. J. (2020). Extrasynaptic CaMKIIα is involved in the antidepressant effects of ketamine by downregulating GluN2B receptors in an LPS-induced depression model. Journal of Neuroinflammation, 17(1), 181. https://doi.org/10.1186/s12974-020-01843-z
Tastan, B., Arioz, B. I., Tufekci, K. U., Tarakcioglu, E., Gonul, C. P., Genc, K., & Genc, S. (2021). Dimethyl fumarate alleviates NLRP3 inflammasome activation in microglia and sickness behavior in LPS-challenged mice. Frontiers in Immunology, 12, 737065. https://doi.org/10.3389/fimmu.2021.737065
Telega, L. M., Berti, R., Blazhenets, G., Domogalla, L.-C., Steinacker, N., Omrane, M. A., Meyer, P. T., Coenen, V. A., Eder, A.-C., & Döbrössy, M. D. (2024). Reserpine-induced rat model for depression: Behavioral, physiological and PET-based dopamine receptor availability validation. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 133, 111013. https://doi.org/10.1016/j.pnpbp.2024.111013
Tonelli, L., Holmes, A. & Postolache, T. (2008). Intranasal Immune Challenge Induces Sex-Dependent Depressive-Like Behavior and Cytokine Expression in the Brain. Neuropsychopharmacol, 33, 1038–1048. https://doi.org/10.1038/sj.npp.1301488
Trullas, R., & Skolnick, P. (1990). Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. European Journal of Pharmacology, 185(1), 1–10. https://doi.org/10.1016/0014-2999(90)90204-j
Tsankova, N., Berton, O., Renthal, W., Kumar, A., Neve, R.L., & Nestler, E.J. (2006). Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nature Neuroscience, 9, 519–525. https://doi.org/10.1038/nn1659
Tuglu, C., Kara, S. H., Caliyurt, O., Zoroglu, S. S., & Savas, H. A. (2003). Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder. Psychopharmacology, 170(4), 429–433. https://doi.org/10.1007/s00213-003-1566-z
Tullis, P. (2021). How ecstasy and psilocybin are shaking up psychiatry. Nature, 589(7834), 506-509. https://doi.org/10.1038/d41586-021-00187-9
Umbricht, D., Niggli, M., Sanwald-Ducray, P., Deptula, D., Moore, R., Grünbauer, W., Boak, L., & Fontoura, P. (2020). Randomized, Double-Blind, Placebo-Controlled Trial of the mGlu2/3 Negative Allosteric Modulator Decoglurant in Partially Refractory Major Depressive Disorder. The Journal of Clinical Psychiatry, 81(4), 18m12470. https://doi.org/10.4088/JCP.18m12470
Vacher, C. M., Tsompanidis, A., Firestein, M. R., & Penn, A. A. (2025). Neuroactive steroid exposure impacts neurodevelopment: Comparison of human and rodent placental contribution. Journal of Neuroendocrinology, 37(7), e13489. https://doi.org/10.1111/jne.13489
Vaishnavi, S. N., Nemeroff, C. B., Plott, S. J., Rao, S. G., Kranzler, J., & Owens, M. J. (2004). Milnacipran: A comparative analysis of human monoamine uptake and transporter binding affinity. Biological Psychiatry, 55(3), 320–322. https://doi.org/10.1016/j.biopsych.2003.07.006
Valdizán, E. M., Díez-Alarcia, R., González-Maeso, J., Pilar-Cuéllar, F., García-Sevilla, J. A., Meana, J. J., & Pazos, A. (2010). α₂-Adrenoceptor functionality in postmortem frontal cortex of depressed suicide victims. Biological Psychiatry, 68(9), 869–872. https://doi.org/10.1016/j.biopsych.2010.07.023
Van Assche, L., Persoons, P., & Vandenbulcke, M. (2014). Neurocognitieve stoornissen in de DSM-5: een kritische bespreking [Neurocognitive disorders in DSM-5: A critical review]. Tijdschrift voor Psychiatrie, 56(3), 211–216.
Varty, G. B., Powell, S. B., Lehmann-Masten, V., Buell, M. R., & Geyer, M. A. (2006). Isolation rearing of mice induces deficits in prepulse inhibition of the startle response. Behavioural Brain Research, 169(1), 162–167. https://doi.org/10.1016/j.bbr.2005.11.025
Veroniki, A. A., Cogo, E., Rios, P., Straus, S. E., Finkelstein, Y., Kealey, R., Reynen, E., Soobiah, C., Thavorn, K., Hutton, B., Hemmelgarn, B. R., Yazdi, F., D’Souza, J., MacDonald, H., & Tricco, A. C. (2017). Comparative safety of anti epileptic drugs during pregnancy: A systematic review and network meta analysis of congenital malformations and prenatal outcomes. BMC Medicine, 15(1), 95. https://doi.org/10.1186/s12916-017-0845-1
Videbech, P., & Ravnkilde, B. (2004). Hippocampal volume and depression: a meta-analysis of MRI studies. The American Journal of Psychiatry, 161(11), 1957–1966. https://doi.org/10.1176/appi.ajp.161.11.1957
von Rotz, R., Schindowski, E. M., Jungwirth, J., Schuldt, A., Rieser, N. M., Zahoranszky, K., Seifritz, E., Nowak, A., Nowak, P., Jäncke, L., Preller, K. H., & Vollenweider, F. X. (2023). Corrigendum to “Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial.” eClinicalMedicine, 56, 101841. https://doi.org/10.1016/j.eclinm.2023.101841
Walker, A., Budac, D., Bisulco, S., Lee, A.W., Smith, R.A., Beenders, B., Kelley, K.W., & Dantzer, R. (2013). NMDA Receptor Blockade by Ketamine Abrogates Lipopolysaccharide-Induced Depressive-Like Behavior in C57BL/6J Mice. Neuropsychopharmacol, 38, 1609–1616. https://doi.org/10.1038/npp.2013.71
Wierońska, J. M., & Pilc, A. (2009). Metabotropic glutamate receptors in the tripartite synapse as a target for new psychotropic drugs. Neurochemistry International, 55(1–3), 85–97. https://doi.org/10.1016/j.neuint.2009.02.019
Wilkinson, L. S., Killcross, S. S., Humby, T., Hall, F. S., Geyer, M. A., & Robbins, T. W. (1994). Social isolation in the rat produces developmentally specific deficits in prepulse inhibition of the acoustic startle response without disrupting latent inhibition. Neuropsychopharmacology, 10(1), 61–72. https://doi.org/10.1038/npp.1994.8
Willner, P. (1984). The validity of animal models of depression. Psychopharmacology, 83(1), 1–16. https://doi.org/10.1007/BF00427414
Willner, P. (2017). The chronic mild stress (CMS) model of depression: History, evaluation, and usage. Neurobiology of Stress, 6, 78–93. https://doi.org/10.1016/j.ynstr.2016.08.002
Witkin, J. M. (2020). mGlu2/3 receptor antagonism: A mechanism to induce rapid antidepressant effects without ketamine associated side effects. Pharmacology, Biochemistry, and Behavior, 190, 172854. https://doi.org/10.1016/j.pbb.2020.172854
Wong, E. Y. H., & Herbert, J. (2006). Raised circulating corticosterone inhibits neuronal differentiation of progenitor cells in the adult hippocampus. Neuroscience, 137(1), 83–92. https://doi.org/10.1016/j.neuroscience.2005.08.073
World Health Organization. (2022). Depression and other common mental disorders: Global health estimates.
Wright, I. K., Upton, N., & Marsden, C. A. (1991). Resocialisation of isolation-reared rats does not alter their anxiogenic profile on the elevated X-maze. Physiology & Behavior, 50(6), 1129–1132. https://doi.org/10.1016/0031-9384(91)90572-6
Wrynn, A. S., Mac Sweeney, C. P., Franconi, F., Lemaire, L., Pouliquen, D., Herlidou, S., Leonard, B. E., Gandon, J., & de Certaines, J. D. (2000). An in-vivo magnetic resonance imaging study of the olfactory bulbectomized rat model of depression. Brain Research, 879(1-2), 193–199. https://doi.org/10.1016/s0006-8993(00)02619-6
Yadid, G., & Friedman, A. (2008). Dynamics of the dopaminergic system as a key component to the understanding of depression. Progress in Brain Research, 172, 265–286. https://doi.org/10.1016/S0079-6123(08)00913-8
Young, G. (2016). DSM-5: Basics and Critics. In: Unifying Causality and Psychology. Springer, Cham. https://doi.org/10.1007/978-3-319-24094-7_22
Zanos, P., & Gould, T. (2018). Mechanisms of ketamine action as an antidepressant. Molecular Psychiatry, 23, 801–811. https://doi.org/10.1038/mp.2017.255
Zanos, P., Highland, J. N., Stewart, B. W., Georgiou, P., Jenne, C. E., Lovett, J., Morris, P. J., Thomas, C. J., Moaddel, R., Zarate, C. A., Jr, & Gould, T. D. (2019). (2R,6R)-hydroxynorketamine exerts mGlu2 receptor-dependent antidepressant actions. Proceedings of the National Academy of Sciences of the United States of America, 116(13), 6441–6450. https://doi.org/10.1073/pnas.1819540116
Zanos, P., Moaddel, R., Morris, P. J., Georgiou, P., Fischell, J., Elmer, G. I., Alkondon, M., Yuan, P., Pribut, H. J., Singh, N. S., Dossou, K. S., Fang, Y., Huang, X. P., Mayo, C. L., Wainer, I. W., Albuquerque, E. X., Thompson, S. M., Thomas, C. J., Zarate, C. A., Jr, & Gould, T. D. (2016). NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature, 533(7604), 481–486. https://doi.org/10.1038/nature17998
Zanos, P., Moaddel, R., Morris, P. J., Riggs, L. M., Highland, J. N., Georgiou, P., Pereira, E. F. R., Albuquerque, E. X., Thomas, C. J., Zarate, C. A., Jr, & Gould, T. D. (2018). Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacological Reviews, 70(3), 621–660. https://doi.org/10.1124/pr.117.015198
Zhang, C., & Marek, G. J. (2008). AMPA receptor involvement in 5-hydroxytryptamine2A receptor-mediated pre-frontal cortical excitatory synaptic currents and DOI-induced head shakes. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 32(1), 62–71. https://doi.org/10.1016/j.pnpbp.2007.07.009
Zhao, X., Zhou, Q., Zhang, H., Ono, M., Furuyama, T., Yamamoto, R., Ishikura, T., Kumai, M., Nakamura, Y., Shiga, H., & Miwa, T., & Kato, N. (2025). Olfactory deprivation promotes amyloid β deposition in a mouse model of Alzheimer’s disease. Brain Research, 1851, 149500. https://doi.org/10.1016/j.brainres.2025.149500
Zhou, W., Wang, N., Yang, C., Li, X.-M., Zhou, Z.-Q., & Yang, J.-J. (2014). Ketamine-induced antidepressant effects are associated with AMPA receptors-mediated upregulation of mTOR and BDNF in rat hippocampus and prefrontal cortex. European Psychiatry, 29(7), 419–423. https://doi.org/10.1016/j.eurpsy.2013.10.005
Zueger, M., Urani, A., Chourbaji, S., Zacher, C., Roche, M., Harkin, A., & Gass, P. (2005). Olfactory bulbectomy in mice induces alterations in exploratory behavior. Neuroscience Letters, 374(2), 142–146. https://doi.org/10.1016/j.neulet.2004.10.040
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