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

被引：3

作者：

Spedding, Michael ^{[1
,2
]}

Sebban, Claude ^{[3
]}

Jay, Therese M. ^{[4
]}

Rocher, Cyril ^{[4
]}

Tesolin-Decros, Brigitte ^{[3
]}

Chazot, Paul ^{[5
]}

Schenker, Esther ^{[1
]}

Szenasi, Gabor ^{[6
,7
]}

Levay, Gyorgy, I ^{[6
,8
,9
]}

Megyeri, Katalin ^{[6
,10
]}

Barkoczy, Jozsef ^{[6
]}

Harsing, Laszlo G. ^{[6
,11
]}

Thomson, Ian ^{[12
]}

Cunningham, Mark O. ^{[12
,13
]}

Whittington, Miles A. ^{[14
]}

Etherington, Lori-An ^{[15
]}

Lambert, Jeremy J. ^{[15
]}

Antoni, Ferenc A. ^{[6
,16
]}

Gacsalyi, Istvan ^{[6
,17
]}

机构：

[1] Inst Rech Internatl Servier, F-92284 Suresnes, France

[2] Spedding Res Solut SAS, F-78110 Le Vesinet, France

[3] Hop Charles Foix, F-94205 Ivry, France

[4] Univ Paris V Descartes, Hop St Anne, INSERM UMR S894, F-75014 Paris, France

[5] Univ Durham, Dept Biosci, Durham DH1 3LE, England

[6] EGIS Pharmaceut Ltd, Behav Pharmacol Lab, H-1106 Budapest, Hungary

[7] Semmelweis Univ, Inst Translat Med, H-1085 Budapest, Hungary

[8] Gedeon Richter Plc, H-1103 Budapest, Hungary

[9] Semmelweis Univ, Fac Hlth Sci, Dept Morphol & Physiol, H-1088 Budapest, Hungary

[10] Hungarian Def Forces Med Ctr, H-1134 Budapest, Hungary

[11] Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, H-1085 Budapest, Hungary

[12] Newcastle Univ, Fac Med Sci, Inst Neurosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[13] Trinity Coll Dublin, Sch Med, Discipline Physiol, Dublin D02 PN40, Ireland

[14] Univ York, Hull York Med Sch, Heslington HU6 7RX, England

[15] Univ Dundee, Ninewells Hosp & Med Sch, Dundee DD1 9SY, Scotland

[16] Univ Edinburgh, Ctr Discovery Brain Sci, Deanery Biomed Sci, Edinburgh EH8 9XD, Midlothian, Scotland

[17] ATRC Aurigon Toxicol Res Ctr Ltd, H-2120 Dunakeszi, Hungary

来源：

CELLS | 2022年 / 11卷 / 07期

关键词：

schizophrenia; EGIS; 11150; S; 36549; theta rhythm; phencyclidine; ketamine; dysconnectivity; COGNITIVE NEUROSCIENCE; SYNAPTIC PLASTICITY; THETA OSCILLATIONS; GAMMA OSCILLATIONS; CONSCIOUS RATS; AMPA-RECEPTOR; SCHIZOPHRENIA; CLOZAPINE; REVERSAL; INCREASES;

D O I：

10.3390/cells11071181

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 >30x lower doses than clozapine, and >100x 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.

引用

页数：21

共 11 条

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