Dual 5-HT3 and 5-HT6 Receptor Antagonist FPPQ Normalizes Phencyclidine-Induced Disruption of Brain Oscillatory Activity in Rats.
5-HT3-R
5-HT6-R
NMDA-R antagonists
Schizophrenia
antipsychotics
Journal
The international journal of neuropsychopharmacology
ISSN: 1469-5111
Titre abrégé: Int J Neuropsychopharmacol
Pays: England
ID NLM: 9815893
Informations de publication
Date de publication:
27 05 2022
27 05 2022
Historique:
received:
08
11
2021
revised:
22
12
2021
accepted:
11
01
2022
pubmed:
14
1
2022
medline:
3
6
2022
entrez:
13
1
2022
Statut:
ppublish
Résumé
Schizophrenia is a severe mental disorder featuring psychotic, depressive, and cognitive alterations. Current antipsychotic drugs preferentially target dopamine D2-R and/or serotonergic 5-HT2A/1A-R. They partly alleviate psychotic symptoms but fail to treat negative symptoms and cognitive deficits. Here we report on the putative antipsychotic activity of (1-[(3-fluorophenyl)sulfonyl]-4-(piperazin-1-yl)-1H-pyrrolo[3,2-c]quinoline dihydrochloride) (FPPQ), a dual serotonin 5-HT3-R/5-HT6-R antagonist endowed with pro-cognitive properties. FPPQ fully reversed phencyclidine-induced decrease of low-frequency oscillations in the medial prefrontal cortex of anaesthetized rats, a fingerprint of antipsychotic activity. This effect was mimicked by the combined administration of the 5-HT3-R and 5-HT6-R antagonists ondansetron and SB-399 885, respectively, but not by either drug alone. In freely moving rats, FPPQ countered phencyclidine-induced hyperlocomotion and augmentation of gamma and high-frequency oscillations in medial prefrontal cortex, dorsal hippocampus, and nucleus accumbens. Overall, this supports that simultaneous blockade of 5-HT3R and 5-HT6-R-like that induced by FPPQ-can be a new target in antipsychotic drug development.
Identifiants
pubmed: 35022720
pii: 6504018
doi: 10.1093/ijnp/pyac003
pmc: PMC9154270
doi:
Substances chimiques
Antipsychotic Agents
0
Quinolines
0
Receptors, Serotonin
0
Serotonin Antagonists
0
serotonin 6 receptor
0
Phencyclidine
J1DOI7UV76
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
425-431Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.
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