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

Autor: Britt T.J. van Hagen, Nick P. van Goethem, Ellis Nelissen, Dean Paes, Karin Koymans, Scott van Hoof, Rudy Schreiber, Mark Varney, Adrian Newman-Tancredi, Jos Prickaerts
Přispěvatelé: RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, Basic Neuroscience 2, Section Psychopharmacology, RS: FPN NPPP II, Cellular and Computational Neuroscience (SILS, FNWI)
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Male
HIGH-EFFICACY
drug effects [Hippocampus]
physiology [Recognition
Psychology]
NLX-101
hippocampus
Neurogenesis
physiology [Hippocampus]
pharmacology [Piperidines]
pharmacology [Aminopyridines]
HIPPOCAMPAL NEUROGENESIS
DESENSITIZATION
pharmacology [Pyrimidines]
Cellular and Molecular Neuroscience
drug effects [Neuronal Plasticity]
SCHIZOPHRENIA
Animals
physiology [Neuronal Plasticity]
ddc:610
Rats
Wistar
Molecular Biology
therapeutic use [Serotonin 5-HT1 Receptor Agonists]
F15599
RECOGNITION
SEROTONIN
PROLIFERATION
physiology [Pattern Recognition
Physiological]
drug effects [Pattern Recognition
Physiological]
Cell Biology
DEPRESSION
F13714
Rats
pharmacology [Serotonin 5-HT1 Receptor Agonists]
DENTATE GYRUS
physiology [Autoreceptors]
Pattern separation
physiology [Receptor
Serotonin
5-HT1A]
5-HT1A
drug effects [Recognition
Psychology]
Zdroj: Molecular and Cellular Neuroscience, 120:103719. Elsevier Science
Molecular and cellular neuroscience, 120:103719. Academic Press Inc.
Molecular and cellular neuroscience 120, 103719 (2022). doi:10.1016/j.mcn.2022.103719
ISSN: 1044-7431
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: