{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T15:49:46Z","timestamp":1782143386130,"version":"3.54.5"},"reference-count":21,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2011,5,9]],"date-time":"2011-05-09T00:00:00Z","timestamp":1304899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:p>\n                    We have validated the use of prolonged inhalation of 7.5% carbon dioxide (CO\n                    <jats:sub>2<\/jats:sub>\n                    ) as a human model of anxiety and have shown that drugs from two prototypical classes of anxiolytics, benzodiazepines and a serotonin reuptake inhibitor, attenuate CO\n                    <jats:sub>2<\/jats:sub>\n                    -induced symptoms ( Bailey et al., 2007a ). Preclinical evidence suggests that drugs acting at the corticotropin-releasing factor (CRF) system may be useful for the treatment of depression, anxiety, and other stress-related disorders ( Valdez, 2006 ), hence we have now examined the effects of a CRF\n                    <jats:sub>1<\/jats:sub>\n                    receptor antagonist in the 7.5% CO\n                    <jats:sub>2<\/jats:sub>\n                    model. In a randomized double-blind, placebo-controlled, study in 32 healthy participants we examined the effects of 7 days of treatment with the CRF\n                    <jats:sub>1<\/jats:sub>\n                    receptor antagonist, R317573, at a dose that shows a favourable safety profile and is comparable with those effective in preclinical models (40\u2009mg). On day 8, eight of the placebo-treated group received lorazepam (LZP) 2\u2009mg as a positive control. All participants underwent 20\u2009min inhalation of 7.5% CO\n                    <jats:sub>2<\/jats:sub>\n                    -enriched air. Subjective reports of peak gas effects were assessed using visual analogue scales and questionnaires. The mean age of participants was 26 years, and 13 were male. The peak effects of CO\n                    <jats:sub>2<\/jats:sub>\n                    were expressed as a difference from baseline scores obtained while breathing air alone. Compared with placebo (PLAC), both drug groups showed a decrease in all subjective symptoms, total score on the panic symptom inventory (CRF 11 [2.6], PLAC 16.4 [3.1], LZP 2.9 [3.0]) and a generalized anxiety disorder symptom scale (CRF 2.2 [1.5], PLAC 8.2 [2.2], LZP 1.1 [1.5]). We have shown that a drug that acts to inhibit the CRF\n                    <jats:sub>1<\/jats:sub>\n                    receptor shows efficacy in the 7.5% CO\n                    <jats:sub>2<\/jats:sub>\n                    model of anxiety in healthy participants.\n                  <\/jats:p>","DOI":"10.1177\/0269881111400650","type":"journal-article","created":{"date-parts":[[2011,5,10]],"date-time":"2011-05-10T01:34:50Z","timestamp":1304991290000},"page":"1199-1206","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":53,"title":["Preliminary evidence of anxiolytic effects of the CRF\n                    <sub>1<\/sub>\n                    receptor antagonist R317573 in the 7.5% CO\n                    <sub>2<\/sub>\n                    proof-of-concept experimental model of human anxiety"],"prefix":"10.1177","volume":"25","author":[{"given":"Jayne E","family":"Bailey","sequence":"first","affiliation":[{"name":"Severnside Alliance for Translational Research (SARTRE), University of Bristol, Bristol, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Papadopoulos","sequence":"additional","affiliation":[{"name":"Psychopharmacology Unit, University of Bristol, Bristol, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Diaper","sequence":"additional","affiliation":[{"name":"Psychopharmacology Unit, University of Bristol, Bristol, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Phillips","sequence":"additional","affiliation":[{"name":"Gloucester Royal Hospital, Gloucester, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ME","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Beerse, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"van der Ark","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Beerse, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin T","family":"Dourish","sequence":"additional","affiliation":[{"name":"P1Vital Ltd, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard R","family":"Dawson","sequence":"additional","affiliation":[{"name":"P1Vital Ltd, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Nutt","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Unit, Centre for Pharmacology and Therapeutics, Division of Experimental Medicine, Imperial College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2011,5,9]]},"reference":[{"key":"bibr1-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4530(01)00075-0"},{"key":"bibr2-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2008.04.002"},{"key":"bibr3-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1002\/da.20048"},{"key":"bibr4-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1177\/0269881111408455"},{"key":"bibr5-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1177\/0269881106063889"},{"key":"bibr6-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1177\/0269881108089603"},{"key":"bibr7-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1177\/0269881106063889"},{"key":"bibr8-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2008.07071199"},{"key":"bibr9-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-10-06340.1995"},{"key":"bibr10-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1002\/da.20695"},{"key":"bibr11-0269881111400650","first-page":"505","volume-title":"Psychopharmacology: The fourth generation of progress","author":"De Souza EB","year":"1995"},{"key":"bibr12-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1037\/1064-1297.15.6.519"},{"key":"bibr13-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301328"},{"key":"bibr14-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1111\/j.0953-8194.2004.01158.x"},{"key":"bibr15-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2006.06.019"},{"key":"bibr16-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-009-1714-1"},{"key":"bibr17-0269881111400650","doi-asserted-by":"crossref","unstructured":"Seddon K, Morris K, Bailey J, Potokar J, Rich A, Wilson S, et al. (2011) Effects of 7.5% CO\n                      2\n                      challenge in generalised anxiety disorder.\n                      J Psychopharmacol\n                      25(1): 43\u201351.","DOI":"10.1177\/0269881110364270"},{"key":"bibr18-0269881111400650","volume-title":"Manual for the State-Trait Anxiety Inventory (Form Y)","author":"Spielberger CD","year":"1983"},{"key":"bibr19-0269881111400650","first-page":"1","volume":"32","author":"Steckler T","year":"2006","journal-title":"Actualit\u00e9s de Chimie Th\u00e9rapeutique, Soci\u00e9t\u00e9 de Chimie Th\u00e9rapeutique"},{"key":"bibr20-0269881111400650","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200620110-00002"},{"key":"bibr21-0269881111400650","doi-asserted-by":"publisher","DOI":"10.1177\/0269881105051527"}],"container-title":["Journal of Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0269881111400650","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0269881111400650","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0269881111400650","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:06:46Z","timestamp":1777507606000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0269881111400650"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5,9]]},"references-count":21,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2011,9]]}},"alternative-id":["10.1177\/0269881111400650"],"URL":"https:\/\/doi.org\/10.1177\/0269881111400650","relation":{},"ISSN":["0269-8811","1461-7285"],"issn-type":[{"value":"0269-8811","type":"print"},{"value":"1461-7285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5,9]]}}}