{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:51:58Z","timestamp":1790779918976,"version":"4.1.0"},"reference-count":70,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T00:00:00Z","timestamp":1562716800000},"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":[[2019,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      NLX-101 (also known as F15599) is a highly selective and efficacious \u2018biased\u2019 agonist at cortical 5-hydroxytryptamine 1A (5-HT\n                      <jats:sub>1A<\/jats:sub>\n                      ) heteroreceptors. In rodents, it possesses marked antidepressant-like activity, potently and completely abolishing immobility in the forced swim test (FST) with extended duration of action.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We investigated the antidepressant-like activity of NLX-101 using the rat chronic mild stress (CMS) model of depression, considered to have a higher translational potential than the FST, as it possesses construct, face and predictive validity. The effects of CMS and repeated NLX-101 treatment were tested using sucrose consumption (a measure of anhedonia), novel object recognition (NOR; a measure of working memory) and elevated plus maze (EPM; a measure of anxiety) tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>NLX-101 reversed the CMS-induced decrease of sucrose intake on day 1 of testing, with full reversal observed at the dose of 0.16 mg\/kg and a less pronounced but still significant effect at 0.04 mg\/kg, both given twice a day intraperitoneally. The effects of NLX-101 were maintained over the 2 week treatment period and persisted for four weeks following cessation of treatment. In the NOR test, both doses of NLX-101 rescued the deficit in discrimination index caused by CMS, without any effect on locomotor activity. However, NLX-101 had no effect on the reduction of open-arms entries produced by CMS in the EPM model. In control, non-stressed rats, NLX-101 produced non-significant effects in all three models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      NLX-101 displayed efficacious activity in the CMS test, with more rapid (1 day) antidepressant-like effects than pharmacological compounds tested previously under the same experimental conditions. These observations suggest that biased agonist targeting of cortical 5-HT\n                      <jats:sub>1A<\/jats:sub>\n                      receptors constitutes a promising strategy to achieve rapid-acting and sustained antidepressant effects.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0269881119860666","type":"journal-article","created":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T05:36:34Z","timestamp":1562736994000},"page":"1456-1466","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":32,"title":["Cortical 5-hydroxytryptamine 1A receptor biased agonist, NLX-101, displays rapid-acting antidepressant-like properties in the rat chronic mild stress model"],"prefix":"10.1177","volume":"33","author":[{"given":"Ronan","family":"Depoort\u00e8re","sequence":"first","affiliation":[{"name":"Neurolixis, Inc., Dana Point, CA, 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