{"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":1790874940700,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T00:00:00Z","timestamp":1559865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R21 NS108722"],"award-info":[{"award-number":["R21 NS108722"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tourette syndrome (<jats:styled-content style=\"fixed-case\">TS<\/jats:styled-content>) is a neuropsychiatric disorder characterised by multiple, persistent tics. These semi\u2010voluntary motor and phonic manifestations are typically aggravated by exposure to acute stress, yet the mechanisms underlying this exacerbation remain unclear. Using a well\u2010characterised animal model of <jats:styled-content style=\"fixed-case\">TS<\/jats:styled-content>, the D1<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>\u20107 mouse, we recently showed that acute stress increases tic\u2010like responses and causes sensorimotor gating deficits, as measured by the prepulse inhibition of the startle. We showed that these effects are promoted by the brain synthesis of the neurosteroid allopregnanolone (<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>). In line with this idea, inhibition of <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> synthesis by finasteride was found to suppress the tic\u2010exacerbating effects of stress; conversely, <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> administration resulted in a marked enhancement of the number of tic\u2010like motor bursts. Given that the primary mechanism of <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> is based on the positive allosteric modulation of <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content><jats:sub>A<\/jats:sub> receptors, in the present study, we hypothesised that the enhancement in tic\u2010like behaviours induced by either stress or <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> may be countered by isoallopregnanolone (iso<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>), the natural 3\u03b2\u2010epimer of <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> that acts as an antagonist to the <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u2010binding site within <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content><jats:sub>A<\/jats:sub> receptors. In agreement with our hypothesis, iso<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> (5\u201010\u00a0mg\u00a0kg<jats:sup>\u20101<\/jats:sup>, <jats:styled-content style=\"fixed-case\">s.c.<\/jats:styled-content>) dose\u2010dependently reduced the number of tic\u2010like behaviours induced by stress in D1<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>\u20107 mice. These effects were comparable to those elicited by both the benchmark <jats:styled-content style=\"fixed-case\">TS<\/jats:styled-content> therapy haloperidol (0.3\u00a0mg\u00a0kg<jats:sup>\u20101<\/jats:sup>, <jats:styled-content style=\"fixed-case\">i.p.<\/jats:styled-content>), as well as finasteride (25\u00a0mg\u00a0kg<jats:sup>\u20101<\/jats:sup>, <jats:styled-content style=\"fixed-case\">i.p.<\/jats:styled-content>). Iso<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> also countered the prepulse inhibition deficits secondary to stress in D1<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>\u20107 mice. Finally, iso<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> opposed the enhancement of tic\u2010like behaviours induced by <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> (15\u00a0mg\u00a0kg<jats:sup>\u20101<\/jats:sup>, <jats:styled-content style=\"fixed-case\">i.p.<\/jats:styled-content>). Given that iso<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> is well\u2010tolerated and has an optimal safety profile, these data suggest that this steroid may have therapeutic properties in <jats:styled-content style=\"fixed-case\">TS<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/jne.12754","type":"journal-article","created":{"date-parts":[[2019,6,8]],"date-time":"2019-06-08T04:32:58Z","timestamp":1559968378000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Isoallopregnanolone reduces tic\u2010like behaviours in the D1<scp>CT<\/scp>\u20107 mouse model of Tourette syndrome"],"prefix":"10.1111","volume":"32","author":[{"given":"Roberto","family":"Cadeddu","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy University of Utah Salt Lake City UT 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