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

Spedding, Michael; Sebban, Claude; Jay, Thérèse M.; Rocher, Cyril; Tesolin-Decros, Brigitte; Chazot, Paul; Schenker, Esther; Szénási, Gabor; Lévay, György I.; Megyeri, Katalin; Barkóczy, Jozsef; Hársing, Laszlo G.; Thomson, Ian; Cunningham, Mark O.; Whittington, Miles A.; Etherington, Lori-An; Lambert, Jeremy J.; Antoni, Ferenc A.; Gacsályi, Istvan

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


Authors

Michael Spedding

Claude Sebban

Thérèse M. Jay

Cyril Rocher

Brigitte Tesolin-Decros

Esther Schenker

Gabor Szénási

György I. Lévay

Katalin Megyeri

Jozsef Barkóczy

Laszlo G. Hársing

Ian Thomson

Mark O. Cunningham

Miles A. Whittington

Lori-An Etherington

Jeremy J. Lambert

Ferenc A. Antoni

Istvan Gacsályi



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.

Citation

Spedding, M., Sebban, C., Jay, T. M., Rocher, C., Tesolin-Decros, B., Chazot, P., …Gacsályi, I. (2022). Phenotypical Screening on Neuronal Plasticity in Hippocampal-Prefrontal Cortex Connectivity Reveals an Antipsychotic with a Novel Profile. Cells, 11(7), Article 1181. https://doi.org/10.3390/cells11071181

Journal Article Type Article
Acceptance Date Mar 28, 2022
Online Publication Date Mar 31, 2022
Publication Date Apr 1, 2022
Deposit Date Apr 1, 2022
Publicly Available Date Apr 1, 2022
Journal Cells
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 11
Issue 7
Article Number 1181
DOI https://doi.org/10.3390/cells11071181

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.





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