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• W2959893596 abstract "Background: NLX-101 (also known as F15599) is a highly selective and efficacious ‘biased’ agonist at cortical 5-hydroxytryptamine 1A (5-HT 1A ) 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. Methods: 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. Results: 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. Conclusions: 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 1A receptors constitutes a promising strategy to achieve rapid-acting and sustained antidepressant effects." @default.
• W2959893596 created "2019-07-23" @default.
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• W2959893596 date "2019-07-10" @default.
• W2959893596 modified "2023-09-27" @default.
• W2959893596 title "Cortical 5-hydroxytryptamine 1A receptor biased agonist, NLX-101, displays rapid-acting antidepressant-like properties in the rat chronic mild stress model" @default.
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• W2959893596 doi "https://doi.org/10.1177/0269881119860666" @default.
• W2959893596 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31290370" @default.
• W2959893596 hasPublicationYear "2019" @default.
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