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However, available treatments are ineffective in around one-third of patients and there is a need for more effective and safer drugs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objectives<\/jats:title>\n                <jats:p>The antidepressant-like and procognitive effects of the \u201cbiased agonists\u201d F15599 (also known as NLX-101) which preferentially targets postsynaptic 5-HT<jats:sub>1A<\/jats:sub> receptors and F13714, which targets 5-HT<jats:sub>1A<\/jats:sub> autoreceptors, were investigated in mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Antidepressant-like properties of the compounds and their effect on cognitive functions were assessed using the forced swim test (FST) and the novel object recognition (NOR), respectively. Next, we induced a depressive-like state by an unpredictable chronic mild stress (UCMS) procedure to test the compounds\u2019 activity in the depression model, followed by measures of sucrose preference, FST, and locomotor activity. Levels of phosphorylated cyclic AMP response element-binding protein (p-CREB) and phosphorylated extracellular signal-regulated kinase (p-ERK1\/2) were also determined.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>F15599 reduced immobility time in the FST over a wider dose-range (2 to 16 mg\/kg po) than F13714 (2 and 4 mg\/kg po), suggesting accentuated antidepressant-like properties in mice. F15599 did not disrupt long-term memory consolidation in the NOR at any dose tested, while F13714 impaired memory formation, notably at higher doses (4\u201316 mg\/kg). In UCMS mice, a single administration of F15599 and F13714 was sufficient to robustly normalize depressive-like behavior in the FST but did not rescue disrupted sucrose preference. Both F15599 and F13714 rescued cortical and hippocampal deficits in p-ERK1\/2 levels of UCMS mice but did not influence the p-CREB levels.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our studies showed that 5-HT<jats:sub>1A<\/jats:sub> receptor biased agonists such as F13714 and especially F15599, due to its less pronounced side effects, might have potential as fast-acting antidepressants.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00213-021-05849-0","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T20:02:45Z","timestamp":1620676965000},"page":"2249-2260","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The selective 5-HT1A receptor biased agonists, F15599 and F13714, show antidepressant-like properties after a single administration in the mouse model of unpredictable chronic mild stress"],"prefix":"10.1007","volume":"238","author":[{"given":"Monika","family":"G\u0142uch-Lutwin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Sa\u0142aciak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Gawalska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Jamrozik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Sniecikowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Newman-Tancredi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Ko\u0142aczkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7134-9515","authenticated-orcid":false,"given":"Karolina","family":"Pytka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"key":"5849_CR1","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1017\/S1461145709991222","volume":"13","author":"M-B Assi\u00e9","year":"2010","unstructured":"Assi\u00e9 M-B, Bardin L, Auclair AL, Carilla-Durand E, Depoort\u00e8re R, Koek W, Kleven MS, Colpaert F, Vacher B, Newman-Tancredi A (2010) F15599, a highly selective post-synaptic 5-HT1A receptor agonist: in-vivo profile in behavioural models of antidepressant and serotonergic activity. 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