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Biased 5-HT1A receptor agonists F13714 and NLX-101 differentially affect pattern separation and neuronal plasticity in rats after acute and chronic treatment.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Biased 5-HT1A receptor agonists F13714 and NLX-101 differentially affect pattern separation and neuronal plasticity in rats after acute and chronic treatment.
Συγγραφείς: van Hagen BTJ; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands., van Goethem NP; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands., Nelissen E; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands., Paes D; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands., Koymans K; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, the Netherlands., van Hoof S; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany., Schreiber R; Faculty of Psychology and Neuroscience, Section Neuropsychology and Psychopharmacology, Maastricht University, Maastricht, the Netherlands., Varney M; Neurolixis Inc., Dana Point, California, USA., Newman-Tancredi A; Neurolixis Inc., Dana Point, California, USA., Prickaerts J; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands. Electronic address: jos.prickaerts@maastrichtuniversity.nl.
Πηγή: Molecular and cellular neurosciences [Mol Cell Neurosci] 2022 May; Vol. 120, pp. 103719. Date of Electronic Publication: 2022 Mar 10.
Τύπος έκδοσης: Journal Article; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Academic Press Country of Publication: United States NLM ID: 9100095 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9327 (Electronic) Linking ISSN: 10447431 NLM ISO Abbreviation: Mol Cell Neurosci Subsets: MEDLINE
Imprint Name(s): Original Publication: San Diego : Academic Press, c1990-
Ιατρικοί όροι (MeSH): Aminopyridines*/pharmacology , Autoreceptors*/physiology , Hippocampus*/drug effects , Hippocampus*/physiology , Neuronal Plasticity*/drug effects , Neuronal Plasticity*/physiology , Pattern Recognition, Physiological*/drug effects , Pattern Recognition, Physiological*/physiology , Piperidines*/pharmacology , Pyrimidines*/pharmacology , Receptor, Serotonin, 5-HT1A*/physiology , Recognition, Psychology*/drug effects , Recognition, Psychology*/physiology , Serotonin 5-HT1 Receptor Agonists*/pharmacology , Serotonin 5-HT1 Receptor Agonists*/therapeutic use, Animals ; Male ; Rats ; Rats, Wistar
Περίληψη: Pattern separation is a hippocampal process in which highly similar stimuli are recognized as separate representations, and deficits could lead to memory impairments in neuropsychiatric disorders such as schizophrenia. The 5-HT1A receptor (5-HT1AR) is believed to be involved in these hippocampal pattern separation processes. However, in the dorsal raphe nucleus (DRN), the 5-HT1AR is expressed as a somatodendritic autoreceptor, negatively regulates serotonergic signaling, and could thereby counteract the effects of hippocampal postsynaptic 5-HT1A receptors. Therefore, this study aims to identify how pre- and post-synaptic 5-HT1AR activity affects pattern separation. Object pattern separation (OPS) performance was measured in male Wistar rats after both acute and chronic treatment (i.p.) with 5-HT1AR biased agonists F13714 (0.0025 mg/kg acutely, 0.02 mg/kg/day chronically) or NLX-101 (0.08 mg/kg acutely, 0.32 mg/kg/day chronically), which preferentially activate autoreceptors or postsynaptic receptors respectively, for 14 days. Body temperature - a functional correlate of hypothalamic 5-HT1AR stimulation - was measured daily. Additionally, 5-HT1AR density (DRN) and plasticity markers (hippocampus) were assessed. Acute treatment with F13714 impaired OPS performance, whereas chronic treatment normalized this, and a drop in body temperature was found from day 4 onwards. NLX-101 enhanced OPS performance acutely and chronically, and caused an acute drop in body temperature. Chronic NLX-101 treatment increased doublecortin positive neurons in the dorsal hippocampus, while chronic treatment with F13714 resulted in a downregulation of 5-HT1A autoreceptors, which likely reversed the acute impairment in OPS performance. Chronic treatment with NLX-101 appears to have therapeutic potential to improve brain plasticity and OPS performance.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Contributed Indexing: Keywords: 5-HT(1A); F13714; NLX-101; Neurogenesis; Pattern separation; hippocampus
Substance Nomenclature: 0 (3-chloro-4-fluorophenyl-(4-fluoro-4-(((5-methyl-6-methylaminopyridin-2-ylmethyl)amino)methyl)piperidin-1-yl)methanone)
0 (3-chloro-4-fluorophenyl-(4-fluoro-4-(((5-methylpyrimidin-2-ylmethyl)amino)methyl)piperidin-1-yl)methanone)
0 (Aminopyridines)
0 (Autoreceptors)
0 (Piperidines)
0 (Pyrimidines)
0 (Serotonin 5-HT1 Receptor Agonists)
112692-38-3 (Receptor, Serotonin, 5-HT1A)
Entry Date(s): Date Created: 20220314 Date Completed: 20220608 Latest Revision: 20220614
Update Code: 20260130
DOI: 10.1016/j.mcn.2022.103719
PMID: 35283305
Βάση Δεδομένων: MEDLINE
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  – Url: https://www.doi.org/10.1016/j.mcn.2022.103719?
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  Data: Biased 5-HT<subscript>1A</subscript> receptor agonists F13714 and NLX-101 differentially affect pattern separation and neuronal plasticity in rats after acute and chronic treatment.
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  Data: <searchLink fieldCode="AU" term="%22van+Hagen+BTJ%22">van Hagen BTJ</searchLink>; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.<br /><searchLink fieldCode="AU" term="%22van+Goethem+NP%22">van Goethem NP</searchLink>; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.<br /><searchLink fieldCode="AU" term="%22Nelissen+E%22">Nelissen E</searchLink>; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.<br /><searchLink fieldCode="AU" term="%22Paes+D%22">Paes D</searchLink>; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.<br /><searchLink fieldCode="AU" term="%22Koymans+K%22">Koymans K</searchLink>; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, the Netherlands.<br /><searchLink fieldCode="AU" term="%22van+Hoof+S%22">van Hoof S</searchLink>; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany.<br /><searchLink fieldCode="AU" term="%22Schreiber+R%22">Schreiber R</searchLink>; Faculty of Psychology and Neuroscience, Section Neuropsychology and Psychopharmacology, Maastricht University, Maastricht, the Netherlands.<br /><searchLink fieldCode="AU" term="%22Varney+M%22">Varney M</searchLink>; Neurolixis Inc., Dana Point, California, USA.<br /><searchLink fieldCode="AU" term="%22Newman-Tancredi+A%22">Newman-Tancredi A</searchLink>; Neurolixis Inc., Dana Point, California, USA.<br /><searchLink fieldCode="AU" term="%22Prickaerts+J%22">Prickaerts J</searchLink>; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands. Electronic address: jos.prickaerts@maastrichtuniversity.nl.
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  Data: <searchLink fieldCode="JN" term="%229100095%22">Molecular and cellular neurosciences</searchLink> [Mol Cell Neurosci] 2022 May; Vol. 120, pp. 103719. <i>Date of Electronic Publication: </i>2022 Mar 10.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Academic+Press%22">Academic Press </searchLink><i>Country of Publication: </i>United States <i>NLM ID: </i>9100095 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1095-9327 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2210447431%22">10447431 </searchLink><i>NLM ISO Abbreviation: </i>Mol Cell Neurosci <i>Subsets: </i>MEDLINE
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  Data: <i>Original Publication</i>: San Diego : Academic Press, c1990-
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– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Pattern separation is a hippocampal process in which highly similar stimuli are recognized as separate representations, and deficits could lead to memory impairments in neuropsychiatric disorders such as schizophrenia. The 5-HT<subscript>1A</subscript> receptor (5-HT<subscript>1A</subscript>R) is believed to be involved in these hippocampal pattern separation processes. However, in the dorsal raphe nucleus (DRN), the 5-HT<subscript>1A</subscript>R is expressed as a somatodendritic autoreceptor, negatively regulates serotonergic signaling, and could thereby counteract the effects of hippocampal postsynaptic 5-HT<subscript>1A</subscript> receptors. Therefore, this study aims to identify how pre- and post-synaptic 5-HT<subscript>1A</subscript>R activity affects pattern separation. Object pattern separation (OPS) performance was measured in male Wistar rats after both acute and chronic treatment (i.p.) with 5-HT<subscript>1A</subscript>R biased agonists F13714 (0.0025 mg/kg acutely, 0.02 mg/kg/day chronically) or NLX-101 (0.08 mg/kg acutely, 0.32 mg/kg/day chronically), which preferentially activate autoreceptors or postsynaptic receptors respectively, for 14 days. Body temperature - a functional correlate of hypothalamic 5-HT<subscript>1A</subscript>R stimulation - was measured daily. Additionally, 5-HT<subscript>1A</subscript>R density (DRN) and plasticity markers (hippocampus) were assessed. Acute treatment with F13714 impaired OPS performance, whereas chronic treatment normalized this, and a drop in body temperature was found from day 4 onwards. NLX-101 enhanced OPS performance acutely and chronically, and caused an acute drop in body temperature. Chronic NLX-101 treatment increased doublecortin positive neurons in the dorsal hippocampus, while chronic treatment with F13714 resulted in a downregulation of 5-HT<subscript>1A</subscript> autoreceptors, which likely reversed the acute impairment in OPS performance. Chronic treatment with NLX-101 appears to have therapeutic potential to improve brain plasticity and OPS performance.<br /> (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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  Data: <i>Keywords: </i>5-HT(1A); F13714; NLX-101; Neurogenesis; Pattern separation; hippocampus
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  Data: 0 (3-chloro-4-fluorophenyl-(4-fluoro-4-(((5-methyl-6-methylaminopyridin-2-ylmethyl)amino)methyl)piperidin-1-yl)methanone)<br />0 (3-chloro-4-fluorophenyl-(4-fluoro-4-(((5-methylpyrimidin-2-ylmethyl)amino)methyl)piperidin-1-yl)methanone)<br />0 (Aminopyridines)<br />0 (Autoreceptors)<br />0 (Piperidines)<br />0 (Pyrimidines)<br />0 (Serotonin 5-HT1 Receptor Agonists)<br />112692-38-3 (Receptor, Serotonin, 5-HT1A)
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  Data: 10.1016/j.mcn.2022.103719
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        Value: 10.1016/j.mcn.2022.103719
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        StartPage: 103719
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      – TitleFull: Biased 5-HT1A receptor agonists F13714 and NLX-101 differentially affect pattern separation and neuronal plasticity in rats after acute and chronic treatment.
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