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

Spedding, Michael and Sebban, Claude and Jay, Thérèse M. and Rocher, Cyril and Tesolin-Decros, Brigitte and Chazot, Paul and Schenker, Esther and Szénási, Gabor and Lévay, György I. and Megyeri, Katalin and Barkóczy, Jozsef and Hársing, Laszlo G. and Thomson, Ian and Cunningham, Mark O. and Whittington, Miles A. and Etherington, Lori-An and Lambert, Jeremy J. and Antoni, Ferenc A. and Gacsályi, Istvan (2022) 'Phenotypical Screening on Neuronal Plasticity in Hippocampal-Prefrontal Cortex Connectivity Reveals an Antipsychotic with a Novel Profile.', Cells, 11 (7). p. 1181.


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.

Item Type:Article
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Publisher 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.
Date accepted:28 March 2022
Date deposited:01 April 2022
Date of first online publication:31 March 2022
Date first made open access:01 April 2022

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