Publication: Dual 5-HT3 and 5-HT6 Receptor Antagonist FPPQ Normalizes Phencyclidine-Induced Disruption of Brain Oscillatory Activity in Rats.
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Date
2022
Authors
Castañé, Anna
Cano, Montserrat
Ruiz-Avila, Luis
Miquel-Rio, Lluís
Celada, Pau
Artigas, Francesc
Riga, Maurizio S
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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
Antipsychotic Agents
Brain
Hippocampus
Nucleus Accumbens
Phencyclidine
Prefrontal Cortex
Quinolines
Rats
Receptors, Serotonin
Serotonin Antagonists
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CIE Terms
Keywords
5-HT3-R, 5-HT6-R, NMDA-R antagonists, Schizophrenia, antipsychotics