{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:29:32Z","timestamp":1785832172901,"version":"3.56.0"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,24]],"date-time":"2021-10-24T00:00:00Z","timestamp":1635033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Fragile X syndrome (FXS) is an X-chromosome-linked dominant genetic disorder that causes a variable degree of cognitive dysfunction and developmental disability. Current treatment is symptomatic and no existing medications target the specific cause of FXS. As with other X-linked disorders, FXS manifests differently in males and females, including abnormalities in the dopamine system that are also seen in Fmr1-knockout (KO) mice. We investigated sex differences in dopamine signaling in Fmr1-KO mice in response to L-stepholidine, a dopamine D1 receptor agonist and D2 receptor antagonist. We found significant sex differences in basal levels of phosphorylated protein kinase A (p-PKA) and glycogen synthase kinase (GSK)-3\u03b2 in wild type mice that were absent in Fmr1-KO mice. In wild-type mice, L-stepholidine increased p-PKA in males but not female mice, decreased p-GSK-3 in female mice and increased p-GSK-3 in male mice. Conversely, in Fmr1-KO mice, L-stepholidine increased p-PKA and p-GSK-3\u03b2 in females, and decreased p-PKA and p-GSK-3\u03b2 in males.<\/jats:p>","DOI":"10.3390\/brainsci11111398","type":"journal-article","created":{"date-parts":[[2021,10,24]],"date-time":"2021-10-24T22:06:16Z","timestamp":1635113176000},"page":"1398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sex Differences in Dopamine Receptor Signaling in Fmr1 Knockout Mice: A Pilot Study"],"prefix":"10.3390","volume":"11","author":[{"given":"Anlong","family":"Jiang","sequence":"first","affiliation":[{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Wang","sequence":"additional","affiliation":[{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin Y. D.","family":"Lu","sequence":"additional","affiliation":[{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Freeman","sequence":"additional","affiliation":[{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Campbell","sequence":"additional","affiliation":[{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Su","sequence":"additional","affiliation":[{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert H. C.","family":"Wong","sequence":"additional","affiliation":[{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"},{"name":"Department of Pharmacology, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada"},{"name":"Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada"},{"name":"Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1097\/YCO.0000000000000131","article-title":"Treatment of the psychiatric problems associated with fragile X syndrome","volume":"28","author":"Hagerman","year":"2015","journal-title":"Curr. 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