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Effect of original anticonvulsant ortho-fluoro-benzonal on immune cells functional properties at chronic ethanol intoxication

Published online by Cambridge University Press:  01 September 2022

E. Markova ,
I. Savkin  and
Т. Shushpanova
E. Markova*
Affiliation:
Federal State Research Institute of Fundamental and Clinical Immunology Russian Academy of Sciences, Neuroimmunology Lab., Novosibirsk, Russian Federation
I. Savkin
Affiliation:
Federal State Research Institute of Fundamental and Clinical Immunology Russian Academy of Sciences, Neuroimmunology Lab., Novosibirsk, Russian Federation
Т. Shushpanova
Affiliation:
Mental Health Research Institute of Tomsk National Investigation MedicalCenter of Russian Academy of Sciences, Clinical Psychoneuroimmunology And Neurobiology, Tomsk, Russian Federation
*
*Corresponding author.

Abstract

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Introduction

GABAa-receptors proved to be the molecular targets of ethanol on immune and nervous cells, potentiating alcohol influence. ortho-Fluoro-benzonal is known to be a circular urea derivative and an artificial ligand of GABA/BD-receptor and thus a potential candidate drug for alchoholism treatment.

Objectives

We have shown the alcohol motivation decrease under ortho-fluoro-benzonal influence in experiment. The investigation of molecular mechanisms and functional targets of this substance is an important step in understanding of molecular pathogenesis and approaches to managing alcohol addiction.

Methods

Splenocytes from male (CBAxC57Bl/6) F1 mice in a state of alcohol dependence owing to 6-month 10% ethanol exposure were aseptically obtained and cultured in presence of GABA, ortho-fluoro-benzonal and mitogens (LPS or concanavalin A). Proliferative activity of immune cells in vitro was estimated by means of radioactive 3H-thymidine incorporation.

Results

The intact animals’ splenocytes revealed increased spontaneous proliferation, increased T-mitogen stimulated and decreased B-mitogen stimulated proliferation in the presence of ortho-fluoro-benzonal. The immune cells from alcoholized animals, demonstrating increased spontaneous proliferative activity and weaken susceptibility to the mitogens, showed normal response patterns, except B-mitogen response case, under ortho-fluoro-benzonal inluence. Addition of GABA into the cultures didn’t cancel most positive effects of ortho-fluoro-benzonal inluence, proving existence of their GABAaR-independent pathways, mediated by other barbiturate receptors in addition to GABAaR-dependent ones.

Conclusions

Immunomodulating properties of artificial GABA receptor ligand, ortho-fluoro-benzonal, in vitro has been shown. The compound may correct immune cells dysregulation caused by chronic ethanol exposure, so the original anticonvulsant has promise in the treatment of alcoholism.

Disclosure

The authors have not supplied a conflict-of-interest statement.

Keywords

original anticonvulsantalchoholismimmune cells
Type
Abstract
Information
European Psychiatry , Volume 65 , Special Issue S1: Abstracts of the 30th European Congress of Psychiatry , June 2022 , pp. S816
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Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of the European Psychiatric Association
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