Phenotypical Screening on Neuronal Plasticity in Hippocampal-Prefrontal Cortex Connectivity Reveals an Antipsychotic with a Novel Profile

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Apr 12

PMID 35406745

Authors

Michael Spedding

Claude Sebban

Therese M Jay

Cyril Rocher

Brigitte Tesolin-Decros

Paul Chazot

Esther Schenker

Gabor Szenasi

Gyorgy I Levay

Katalin Megyeri

Jozsef Barkoczy

Laszlo G Harsing Jr

Ian Thomson

Mark O Cunningham

Miles A Whittington

Lori-An Etherington

Jeremy J Lambert

Ferenc A Antoni

Istvan Gacsalyi

Affiliations

Soon will be listed here.

Abstract

Dysfunction in the hippocampus-prefrontal cortex (H-PFC) circuit is a critical determinant of schizophrenia. Screening of pyridazinone-risperidone hybrids on this circuit revealed EGIS 11150 (S 36549). EGIS 11150 induced theta rhythm in hippocampal slice preparations in the stratum lacunosum molecular area of CA1, which was resistant to atropine and prazosin. EGIS 11150 enhanced H-PFC coherence, and increased the 8−9 Hz theta band of the EEG power spectrum (from 0.002 mg/kg i.p, at >30× lower doses than clozapine, and >100× for olanzapine, risperidone, or haloperidol). EGIS 11150 fully blocked the effects of phencyclidine (PCP) or ketamine on EEG. Inhibition of long-term potentiation (LTP) in H-PFC was blocked by platform stress, but was fully restored by EGIS 11150 (0.01 mg/kg i.p.), whereas clozapine (0.3 mg/kg ip) only partially restored LTP. EGIS 11150 has a unique electrophysiological profile, so phenotypical screening on H-PFC connectivity can reveal novel antipsychotics.

Citing Articles

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