{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:04:01Z","timestamp":1785438241112,"version":"3.56.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST105\u20102320\u2010B\u2010002\u2010059\u2010MY3"],"award-info":[{"award-number":["MOST105\u20102320\u2010B\u2010002\u2010059\u2010MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Sleep Research"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Adenosine exhibits a somnogenic effect; however, there is no adenosinergic hypnotic because of cardiovascular effects. This study investigated whether N6\u2010(4\u2010hydroxybenzyl) adenine riboside (T1\u201011), extracted from <jats:italic>Gastrodia elata<\/jats:italic>, produces somnogenic effects in rodents. We determined the involvement of adenosine 2A receptors (A2ARs) in GABAergic neurons of the ventrolateral preoptic area (VLPO) and the cardiovascular effects. Change of cage bedding is employed as a stressor to induce insomnia in rodents, and electroencephalograms and electromyograms were used to acquire and analyse sleep\u2013wake activity. We found that intracerebroventricular administration of T1\u201011 before a dark period increased non\u2010rapid eye movement (NREM) and rapid eye movement (REM) sleep during a dark period, and T1\u201011\u2010induced sleep increases were blocked by the A2AR antagonist, SCH58261, in na\u00efve rats. Oral administration of T1\u201011 increased NREM sleep during both dark and light periods. Microinjection of the A2AR antagonist, SCH58261, into the VLPO blocked sleep effects of T1\u201011. In addition to the somnogenic effect in na\u00efve mice, T1\u201011 suppressed the stress\u2010induced insomnia and this suppressive effect was blocked by SCH58261. C\u2010fos expression in GABAergic neurons of VLPO was increased after administration of T1\u201011 in Gad2\u2010Cre::Ai14 mice, suggesting the activation of GABAergic neurons in the VLPO. T1\u201011 exhibited no effects on heart rate and the low frequency\/high frequency ratio of heart rate variability. We concluded that T1\u201011 elicited somnogenic effects and effectively ameliorated acute stress\u2010induced insomnia. The somnogenic effect is mediated by A2ARs to activate GABAergic neurons in the VLPO. This adenosine analogue could be a potential hypnotic because of no sympathetic and parasympathetic effects on the cardiovascular system.<\/jats:p>","DOI":"10.1111\/jsr.13156","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T04:53:58Z","timestamp":1596516838000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effects of N<sup>6<\/sup>\u2010(4\u2010hydroxybenzyl) adenine riboside in stress\u2010induced insomnia in rodents"],"prefix":"10.1111","volume":"30","author":[{"given":"Shuo\u2010Bin","family":"Jou","sequence":"first","affiliation":[{"name":"Department of Neurology Mackay Medical College Mackay Memorial Hospital New Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung\u2010Jen","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine School of Veterinary Medicine National Taiwan University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Ying","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine School of Veterinary Medicine National Taiwan University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Lu","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Sport Management College of Tourism, Leisure and Sports Aletheia University New Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0271-5416","authenticated-orcid":false,"given":"Fang\u2010Chia","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine School of Veterinary Medicine National Taiwan University Taipei Taiwan"},{"name":"Graduate Institute of Brain and Mind Sciences College of Medicine National Taiwan University Taipei Taiwan"},{"name":"Graduate Institute of Acupuncture Science College of Chinese Medicine China Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00679.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(99)00219-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2004.06.004"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1809-08.2008"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1998.275.3.R793"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2225-4110(16)30054-2"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15561.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1970.sp009220"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.05.045"},{"issue":"12","key":"e_1_2_9_11_1","first-page":"1061","article-title":"Therapeutic potential of Gastrodia elata Blume for the treatment of Alzheimer\u2019s disease","volume":"8","author":"Huang G. 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