Castañé, AnnaCano, MontserratRuiz-Avila, LuisMiquel-Rio, LluísCelada, PauArtigas, FrancescRiga, Maurizio S2023-05-032023-05-032022http://hdl.handle.net/10668/19801Schizophrenia 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.enAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/5-HT3-R5-HT6-RNMDA-R antagonistsSchizophreniaantipsychoticsAnimalsAntipsychotic AgentsBrainHippocampusNucleus AccumbensPhencyclidinePrefrontal CortexQuinolinesRatsReceptors, SerotoninSerotonin Antagonistsresearch article35022720open access10.1093/ijnp/pyac0031469-5111PMC9154270https://academic.oup.com/ijnp/article-pdf/25/5/425/43846911/pyac003.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154270/pdf