{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T12:29:55Z","timestamp":1782476995811,"version":"3.54.5"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K07333"],"award-info":[{"award-number":["19K07333"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1007\/s00210-025-04306-5","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T07:30:30Z","timestamp":1748849430000},"page":"17033-17041","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Progesterone- and deoxycorticosterone-derived GABAergic neurosteroids induce itch-related scratching behavior in mouse model of atopic dermatitis"],"prefix":"10.1007","volume":"398","author":[{"given":"Rina","family":"Tanaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"4306_CR1","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.pnpbp.2013.09.005","volume":"48","author":"A Bali","year":"2014","unstructured":"Bali A, Jaggi AS (2014) Multifunctional aspects of allopregnanolone in stress and related disorders. Prog Neuropsychopharmacol Biol Psychiatry 48:64\u201378. https:\/\/doi.org\/10.1016\/j.pnpbp.2013.09.005","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"4306_CR2","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/0248-4900(91)90045-O","volume":"71","author":"EE Baulieu","year":"1991","unstructured":"Baulieu EE (1991) Neurosteroids: a new function in the brain. Biol Cell 71:3\u201310. https:\/\/doi.org\/10.1016\/0248-4900(91)90045-O","journal-title":"Biol Cell"},{"key":"4306_CR3","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1056\/NEJMoa1314768","volume":"371","author":"LA Beck","year":"2014","unstructured":"Beck LA, Tha\u00e7i D, Hamilton JD, Graham NM, Bieber T, Rocklin R, Ming JE, Ren H, Kao R, Simpson E, Ardeleanu M, Weinstein SP, Pirozzi G, Guttman-Yassky E, Su\u00e1rez-Fari\u00f1as M, Hager MD, Stahl N, Yancopoulos GD, Radin AR (2014) Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med 371:130\u2013139. https:\/\/doi.org\/10.1056\/NEJMoa1314768","journal-title":"N Engl J Med"},{"key":"4306_CR4","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1124\/jpet.115.229302","volume":"357","author":"CM Carver","year":"2016","unstructured":"Carver CM, Reddy DS (2016) Neurosteroid Structure-Activity Relationships for Functional Activation of Extrasynaptic \u03b4GABA(A) Receptors. J Pharmacol Exp Ther 357:188\u2013204. https:\/\/doi.org\/10.1124\/jpet.115.229302","journal-title":"J Pharmacol Exp Ther"},{"key":"4306_CR5","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1016\/j.jaci.2013.10.048","volume":"133","author":"F Cevikbas","year":"2014","unstructured":"Cevikbas F, Wang X, Akiyama T, Kempkes C, Savinko T, Antal A, Kukova G, Buhl T, Ikoma A, Buddenkotte J, Soumelis V, Feld M, Alenius H, Dillon SR, Carstens E, Homey B, Basbaum A, Steinhoff M (2014) A sensory neuron-expressed IL-31 receptor mediates T helper cell-dependent itch: Involvement of TRPV1 and TRPA1. J Allergy Clin Immunol 133:448\u2013460. https:\/\/doi.org\/10.1016\/j.jaci.2013.10.048","journal-title":"J Allergy Clin Immunol"},{"key":"4306_CR6","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1124\/jpet.110.178244","volume":"337","author":"DE Earl","year":"2011","unstructured":"Earl DE, Tietz EI (2011) Inhibition of recombinant L-type voltage-gated calcium channels by positive allosteric modulators of GABAA receptors. J Pharmacol Exp Ther 337:301\u2013311. https:\/\/doi.org\/10.1124\/jpet.110.178244","journal-title":"J Pharmacol Exp Ther"},{"key":"4306_CR7","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1248\/bpb.b19-00088","volume":"43","author":"M Fujii","year":"2020","unstructured":"Fujii M (2020) Current understanding of pathophysiological mechanisms of atopic dermatitis: interactions among skin barrier dysfunction, immune abnormalities and pruritus. Biol Pharm Bull 43:12\u201319. https:\/\/doi.org\/10.1248\/bpb.b19-00088","journal-title":"Biol Pharm Bull"},{"key":"4306_CR8","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1111\/j.0906-6705.2005.00313.x","volume":"14","author":"M Fujii","year":"2005","unstructured":"Fujii M, Tomozawa J, Mizutani N, Nabe T, Danno K, Kohno S (2005) Atopic dermatitis-like pruritic skin inflammation caused by feeding a special diet to HR-1 hairless mice. Exp Dermatol 14:460\u2013468. https:\/\/doi.org\/10.1111\/j.0906-6705.2005.00313.x","journal-title":"Exp Dermatol"},{"key":"4306_CR9","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.ejphar.2009.03.051","volume":"611","author":"M Fujii","year":"2009","unstructured":"Fujii M, Nakamura T, Fukuno S, Mizutani N, Nabe T, Kohno S (2009) Ethanol aggravates itch-related scratching in hairless mice developing atopic dermatitis. Eur J Pharmacol 611:92\u201399. https:\/\/doi.org\/10.1016\/j.ejphar.2009.03.051","journal-title":"Eur J Pharmacol"},{"key":"4306_CR10","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1111\/exd.12592","volume":"24","author":"M Fujii","year":"2015","unstructured":"Fujii M, Shimazaki Y, Muto Y, Kohno S, Ohya S, Nabe T (2015) Dietary deficiencies of unsaturated fatty acids and starch cause atopic dermatitis-like pruritus in hairless mice. Exp Dermatol 24:108\u2013113. https:\/\/doi.org\/10.1111\/exd.12592","journal-title":"Exp Dermatol"},{"key":"4306_CR11","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.ejphar.2018.08.018","volume":"836","author":"M Fujii","year":"2018","unstructured":"Fujii M, Takeuchi K, Umehara Y, Takeuchi M, Nakayama T, Ohgami S, Asano E, Nabe T, Ohya S (2018) Barbiturates enhance itch-associated scratching in atopic dermatitis mice: A possible clue to understanding nocturnal pruritus in atopic dermatitis. Eur J Pharmacol 836:57\u201366. https:\/\/doi.org\/10.1016\/j.ejphar.2018.08.018","journal-title":"Eur J Pharmacol"},{"key":"4306_CR12","doi-asserted-by":"publisher","first-page":"2364","DOI":"10.1038\/s41598-019-38858-3","volume":"9","author":"M Fujii","year":"2019","unstructured":"Fujii M, Ohgami S, Asano E, Nakayama T, Toda T, Nabe T, Ohya S (2019) Brain allopregnanolone induces marked scratching behaviour in diet-induced atopic dermatitis mouse model. Sci Rep 9:2364. https:\/\/doi.org\/10.1038\/s41598-019-38858-3","journal-title":"Sci Rep"},{"key":"4306_CR13","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.pharmthera.2007.05.006","volume":"116","author":"SS Girdler","year":"2007","unstructured":"Girdler SS, Klatzkin R (2007) Neurosteroids in the context of stress: implications for depressive disorders. Pharmacol Ther 116:125\u2013139. https:\/\/doi.org\/10.1016\/j.pharmthera.2007.05.006","journal-title":"Pharmacol Ther"},{"key":"4306_CR14","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1056\/NEJMoa1917006","volume":"383","author":"Kabashima K, Matsumura T, Komazaki H, Kawashima M, Nemolizumab-JP01 Study Group","year":"2020","unstructured":"Kabashima K, Matsumura T, Komazaki H, Kawashima M, Nemolizumab-JP01 Study Group (2020) Trial of Nemolizumab and Topical Agents for Atopic Dermatitis with Pruritus. N Engl J Med 383:141\u2013150. https:\/\/doi.org\/10.1056\/NEJMoa1917006","journal-title":"N Engl J Med"},{"key":"4306_CR15","doi-asserted-by":"publisher","first-page":"S109","DOI":"10.1016\/s0091-6749(99)70052-7","volume":"104","author":"CS Koblenzer","year":"1999","unstructured":"Koblenzer CS (1999) Itching and the atopic skin. J Allergy Clin Immunol 104:S109\u2013S113. https:\/\/doi.org\/10.1016\/s0091-6749(99)70052-7","journal-title":"J Allergy Clin Immunol"},{"key":"4306_CR16","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1016\/S0022-3565(25)22531-9","volume":"270","author":"TG Kokate","year":"1994","unstructured":"Kokate TG, Svensson BE, Rogawski MA (1994) Anticonvulsant activity of neurosteroids: correlation with gamma-aminobutyric acid-evoked chloride current potentiation. J Pharmacol Exp Ther 270:1223\u2013229","journal-title":"J Pharmacol Exp Ther"},{"key":"4306_CR17","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/epi.12025","volume":"53","author":"W L\u00f6scher","year":"2012","unstructured":"L\u00f6scher W, Rogawski MA (2012) How theories evolved concerning the mechanism of action of barbiturates. Epilepsia 53:12\u201325. https:\/\/doi.org\/10.1111\/epi.12025","journal-title":"Epilepsia"},{"key":"4306_CR18","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1016\/j.it.2018.10.001","volume":"39","author":"MR Mack","year":"2018","unstructured":"Mack MR, Kim BS (2018) The itch-scratch cycle: a neuroimmune perspective. Trends Immunol 39:980\u2013991. https:\/\/doi.org\/10.1016\/j.it.2018.10.001","journal-title":"Trends Immunol"},{"key":"4306_CR19","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1126\/science.2422758","volume":"232","author":"MD Majewska","year":"1986","unstructured":"Majewska MD, Harrison NL, Schwartz RD, Barker JL, Paul SM (1986) Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science 232:1004\u20131007. https:\/\/doi.org\/10.1126\/science.2422758","journal-title":"Science"},{"key":"4306_CR20","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1111\/jdv.19580","volume":"38","author":"A Marani","year":"2024","unstructured":"Marani A, Bianchelli T, Gesuita R, Faragalli A, Foti C, Malara G, Micali G, Amerio P, Rongioletti F, Corazza M, Patrizi A, Peris K, Pimpinelli N, Parodi A, Fargnoli MC, Cannavo SP, Pigatto P, Pellacani G, Ferrucci SM, Argenziano G, Cusano F, Stingeni L, Potenza MC, Romanelli M, Bianchi L, Offidani A, Campanati A, Collaborators, (2024) Gender differences in adult atopic dermatitis and clinical implication: Results from a nationwide multicentre study. J Eur Acad Dermatol Venereol 38:375\u2013383. https:\/\/doi.org\/10.1111\/jdv.19580","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"4306_CR21","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1038\/nsmb.3484","volume":"24","author":"PS Miller","year":"2017","unstructured":"Miller PS, Scott S, Masiulis S, De Colibus L, Pardon E, Steyaert J, Aricescu AR (2017) Structural basis for GABAA receptor potentiation by neurosteroids. Nat Struct Mol Biol 24:986\u2013992. https:\/\/doi.org\/10.1038\/nsmb.3484","journal-title":"Nat Struct Mol Biol"},{"key":"4306_CR22","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.alit.2016.10.005","volume":"66","author":"H Murota","year":"2017","unstructured":"Murota H, Katayama I (2017) Exacerbating factors of itch in atopic dermatitis. Allergol Int 66:8\u201313. https:\/\/doi.org\/10.1016\/j.alit.2016.10.005","journal-title":"Allergol Int"},{"key":"4306_CR23","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1124\/mol.117.108563","volume":"92","author":"AM Nik","year":"2017","unstructured":"Nik AM, Pressly B, Singh V, Antrobus S, Hulsizer S, Rogawski MA, Wulff H, Pessah IN (2017) Rapid Throughput Analysis of GABAA Receptor Subtype Modulators and Blockers Using DiSBAC1(3) Membrane Potential Red Dye. Mol Pharmacol 92:88\u201399. https:\/\/doi.org\/10.1124\/mol.117.108563","journal-title":"Mol Pharmacol"},{"key":"4306_CR24","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.cell.2017.08.006","volume":"171","author":"LK Oetjen","year":"2017","unstructured":"Oetjen LK, Mack MR, Feng J, Whelan TM, Niu H, Guo CJ, Chen S, Trier AM, Xu AZ, Tripathi SV, Luo J, Gao X, Yang L, Hamilton SL, Wang PL, Brestoff JR, Council ML, Brasington R, Schaffer A, Brombacher F, Hsieh CS, Gereau RW, Miller MJ, Chen ZF, Hu H, Davidson S, Liu Q, Kim BS (2017) Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch. Cell 171:217-228.e13. https:\/\/doi.org\/10.1016\/j.cell.2017.08.006","journal-title":"Cell"},{"key":"4306_CR25","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/0896-6273(90)90202-q","volume":"4","author":"G Puia","year":"1990","unstructured":"Puia G, Santi MR, Vicini S, Pritchett DB, Purdy RH, Paul SM, Seeburg PH, Costa E (1990) Neurosteroids act on recombinant human GABAA receptors. Neuron 4:759\u2013765. https:\/\/doi.org\/10.1016\/0896-6273(90)90202-q","journal-title":"Neuron"},{"key":"4306_CR26","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1615\/critrevneurobiol.v15.i34.20","volume":"15","author":"DS Reddy","year":"2003","unstructured":"Reddy DS (2003) Pharmacology of endogenous neuroactive steroids. Crit Rev Neurobiol 15:197\u2013234. https:\/\/doi.org\/10.1615\/critrevneurobiol.v15.i34.20","journal-title":"Crit Rev Neurobiol"},{"key":"4306_CR27","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.nbd.2014.06.010","volume":"72","author":"DS Reddy","year":"2014","unstructured":"Reddy DS (2014) Neurosteroids and their role in sex-specific epilepsies. Neurobiol Dis 72:198\u2013209. https:\/\/doi.org\/10.1016\/j.nbd.2014.06.010","journal-title":"Neurobiol Dis"},{"key":"4306_CR28","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1002\/jnr.23853","volume":"95","author":"DS Reddy","year":"2017","unstructured":"Reddy DS (2017) Sex differences in the anticonvulsant activity of neurosteroids. J Neurosci Res 95:661\u2013670. https:\/\/doi.org\/10.1002\/jnr.23853","journal-title":"J Neurosci Res"},{"key":"4306_CR29","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.tips.2016.04.003","volume":"37","author":"DS Reddy","year":"2016","unstructured":"Reddy DS, Estes WA (2016) Clinical Potential of Neurosteroids for CNS Disorders. Trends Pharmacol Sci 37:543\u2013561. https:\/\/doi.org\/10.1016\/j.tips.2016.04.003","journal-title":"Trends Pharmacol Sci"},{"key":"4306_CR30","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1124\/jpet.110.169854","volume":"334","author":"DS Reddy","year":"2010","unstructured":"Reddy DS, Jian K (2010) The testosterone-derived neurosteroid androstanediol is a positive allosteric modulator of GABAA receptors. J Pharmacol Exp Ther 334:1031\u20131041. https:\/\/doi.org\/10.1124\/jpet.110.169854","journal-title":"J Pharmacol Exp Ther"},{"key":"4306_CR31","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1056\/NEJMra2023911","volume":"384","author":"S St\u00e4nder","year":"2021","unstructured":"St\u00e4nder S (2021) Atopic dermatitis. N Engl J Med 384:1136\u20131143. https:\/\/doi.org\/10.1056\/NEJMra2023911","journal-title":"N Engl J Med"},{"key":"4306_CR32","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1034\/j.1600-0625.2002.110102.x","volume":"11","author":"S St\u00e4nder","year":"2002","unstructured":"St\u00e4nder S, Steinhoff M (2002) Pathophysiology of pruritus in atopic dermatitis: an overview. Exp Dermatol 11:12\u201324. https:\/\/doi.org\/10.1034\/j.1600-0625.2002.110102.x","journal-title":"Exp Dermatol"},{"key":"4306_CR33","doi-asserted-by":"publisher","first-page":"4071","DOI":"10.1073\/pnas.83.11.4071","volume":"83","author":"PD Suzdak","year":"1986","unstructured":"Suzdak PD, Schwartz RD, Skolnick P, Paul SM (1986) Ethanol stimulates gamma-aminobutyric acid receptor-mediated chloride transport in rat brain synaptoneurosomes. Proc Natl Acad Sci U S A 83:4071\u20134075. https:\/\/doi.org\/10.1073\/pnas.83.11.4071","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4306_CR34","doi-asserted-by":"publisher","first-page":"886","DOI":"10.2174\/1570159X19666211202150041","volume":"20","author":"L Wang","year":"2022","unstructured":"Wang L, Covey DF, Akk G, Evers AS (2022) Neurosteroid Modulation of GABAA Receptor Function by Independent Action at Multiple Specific Binding Sites. Curr Neuropharmacol 20:886\u2013890. https:\/\/doi.org\/10.2174\/1570159X19666211202150041","journal-title":"Curr Neuropharmacol"},{"key":"4306_CR35","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1210\/mend.12.9.0163","volume":"12","author":"CH Wetzel","year":"1998","unstructured":"Wetzel CH, Hermann B, Behl C, Pestel E, Rammes G, Zieglg\u00e4nsberger W, Holsboer F, Rupprecht R (1998) Functional antagonism of gonadal steroids at the 5-hydroxytryptamine type 3 receptor. Mol Endocrinol 12:1441\u20131451. https:\/\/doi.org\/10.1210\/mend.12.9.0163","journal-title":"Mol Endocrinol"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-04306-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-025-04306-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-04306-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T04:29:15Z","timestamp":1764822555000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-025-04306-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,2]]},"references-count":35,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["4306"],"URL":"https:\/\/doi.org\/10.1007\/s00210-025-04306-5","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,2]]},"assertion":[{"value":"23 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Animal Research of Kyoto Pharmaceutical University (approval number: PCOL-20-004).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}]}}