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

View record from ScienceDirect

καταχωρήστε σχόλιο πρώτοι!