Publication:
Dual 5-HT3 and 5-HT6 Receptor Antagonist FPPQ Normalizes Phencyclidine-Induced Disruption of Brain Oscillatory Activity in Rats.

Loading...
Thumbnail Image

Date

2022

Authors

Castañé, Anna
Cano, Montserrat
Ruiz-Avila, Luis
Miquel-Rio, Lluís
Celada, Pau
Artigas, Francesc
Riga, Maurizio S

Advisors

Journal Title

Journal ISSN

Volume Title

Publisher

Metrics
Google Scholar
Export

Research Projects

Organizational Units

Journal Issue

Abstract

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.

Description

MeSH Terms

Animals
Antipsychotic Agents
Brain
Hippocampus
Nucleus Accumbens
Phencyclidine
Prefrontal Cortex
Quinolines
Rats
Receptors, Serotonin
Serotonin Antagonists

DeCS Terms

CIE Terms

Keywords

5-HT3-R, 5-HT6-R, NMDA-R antagonists, Schizophrenia, antipsychotics

Citation