{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:15:40Z","timestamp":1790874940164,"version":"4.1.0"},"reference-count":191,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T00:00:00Z","timestamp":1629590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21NS108722"],"award-info":[{"award-number":["R21NS108722"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21DA049530"],"award-info":[{"award-number":["R21DA049530"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The neurosteroid allopregnanolone (3\u03b1\u2010hydroxy\u20105\u03b1\u2010pregnan\u201020\u2010one; AP) elicits pleiotropic effects in the central nervous system, ranging from neuroprotective and anti\u2010inflammatory functions to the regulation of mood and emotional responses. Several lines of research show that the brain rapidly produces AP in response to acute stress to reduce the allostatic load and enhance coping. These effects not only are likely mediated by GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptor activation but also result from the contributions of other mechanisms, such as the stimulation of membrane progesterone receptors. In keeping with this evidence, AP has been shown to exert rapid, potent antidepressant properties and has been recently approved for the therapy of moderate\u2010to\u2010severe postpartum depression. In addition to depression, emerging evidence points to the potential of AP as a therapy for other neuropsychiatric disorders, including anxiety, seizures, post\u2010traumatic stress disorder and cognitive problems. Although this evidence has spurred interest in further therapeutic applications of AP, some investigations suggest that this neurosteroid may also be associated with adverse events in specific disorders. For example, our group has recently documented that AP increases tic\u2010like manifestations in several animal models of tic disorders; furthermore, our results indicate that inhibiting AP synthesis and signalling reduces the exacerbation of tic severity associated with acute stress. Although the specific mechanisms of these effects remain partially elusive, our findings point to the possibility that the GABAergic activation by AP may also lead to disinhibitory effects, which could interfere with the ability of patients to suppress their tics. Future studies will be necessary to verify whether these mechanisms may apply to other externalising manifestations, such as impulse\u2010control problems and manic symptoms.\n                  <\/jats:p>","DOI":"10.1111\/jne.13022","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T14:51:07Z","timestamp":1627656667000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Allopregnanolone: The missing link to explain the effects of stress on tic exacerbation?"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4498-9637","authenticated-orcid":false,"given":"Marco","family":"Bortolato","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy University of Utah  Salt Lake City UT USA"},{"name":"Research Consortium on NeuroEndocrine Causes of Tics (ReConNECT)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara J.","family":"Coffey","sequence":"additional","affiliation":[{"name":"Research Consortium on NeuroEndocrine Causes of Tics (ReConNECT)"},{"name":"Department of Psychiatry and Behavioral Science Miller School of Medicine University of Miami  Miami FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilma","family":"Gabbay","sequence":"additional","affiliation":[{"name":"Research Consortium on NeuroEndocrine Causes of Tics (ReConNECT)"},{"name":"Department of Psychiatry and Behavioral Sciences Albert Einstein College of Medicine  Bronx NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0229-6090","authenticated-orcid":false,"given":"Simona","family":"Scheggi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Medicine School of Medicine University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606544103"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161211795049589"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2422758"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05324"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2007.03.011"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1703"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","unstructured":"CarverCM ReddyDS.Neurosteroid interactions with synaptic and extrasynaptic GABA(A) receptors: regulation of subunit plasticity phasic and tonic inhibition and neuronal network excitability [published correction appears in Psychopharmacology 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