Changes in serotonin neurotransmission as assayed by microdialysis after acute, intermittent or chronic ethanol administration and withdrawal

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY Fundamental & Clinical Pharmacology Pub Date : 2023-09-15 DOI:10.1111/fcp.12949

Abdelkader Dahchour, Roberta J. Ward

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Abstract

Background

The serotonergic neurotransmitter system is involved in many ethanol-induced changes, including many behavioural alterations, as well as contributing to alcohol dependence and its withdrawal.

Aims

This review has evaluated microdialysis studies where alterations in the serotonin system, that is, serotonin, 5-HT, or its metabolite 5-hydroxyindoleacetic acid, 5-HIAA, have been reported during different ethanol intoxication states, as well as in animals showing alcohol preference or not. Changes in 5-HT receptors and the 5-HT transporter are briefly reviewed to comprehend the significance of changes in microdialysate 5-HT concentrations.

Materials and methods

Changes in 5-HT content following acute, chronic and during ethanol withdrawal states are evaluated. In addition, the serotoninergic system was assessed in animals that have been genetically selected for alcohol preference to ascertain whether changes in this monoamine microdialysate content may contribute to alcohol preference.

Results and discussion

Changes occurred in 5-HT signalling in the limbic brain regions, increasing after acute ethanol administration in specific brain regions, particularly at higher doses, while chronic alcohol exposure essentially decreased serotonergic transmission. Such changes may play a pivotal role in emotion-driven craving and relapse. Depending on the dosage, mode of administration and consumption rate, ethanol affects specific brain regions in different ways, enhancing or reducing 5-HT microdialysate content, thereby inducing behavioural and cognitive functions and enhancing ethanol consumption.

Conclusion

Microdialysis studies demonstrated that ethanol induces several alterations in 5-HT content as well as its metabolites, 5-HIAA and 5-HTOL, not only in its release from a specific brain region but also in the modifications of its different receptor subtypes and its transporter.

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急性、间歇或慢性乙醇给药和停药后通过微透析测定5-羟色胺神经传递的变化。

背景：5-羟色胺能神经递质系统参与了许多乙醇诱导的变化，包括许多行为改变，以及导致酒精依赖和戒断。目的：这篇综述评估了微透析研究，其中在不同的乙醇中毒状态下，以及在表现出酒精偏好与否的动物中，5-羟色胺系统，即5-羟色胺，5-HT或其代谢产物5-羟基吲哚乙酸，5-HIAA发生了改变。简要回顾了5-HT受体和5-HT转运蛋白的变化，以了解微透析液5-HT浓度变化的意义。材料和方法：评估急性、慢性和乙醇戒断状态下5-HT含量的变化。此外，还对经过基因选择的酒精偏好动物的血清素能系统进行了评估，以确定这种单胺微透析液含量的变化是否有助于酒精偏好。结果和讨论：边缘脑区域的5-HT信号发生变化，在特定脑区域急性乙醇给药后增加，特别是在更高剂量下，而慢性酒精暴露基本上减少了5-羟色胺能的传播。这种变化可能在情绪驱动的渴望和复发中发挥关键作用。根据剂量、给药方式和消耗率的不同，乙醇以不同的方式影响特定的大脑区域，增加或减少5-HT微透析液的含量，从而诱导行为和认知功能，并增加乙醇消耗。结论：微透析研究表明，乙醇诱导5-HT含量及其代谢产物5-HIAA和5-HTOL的几种变化，不仅在其从特定脑区的释放方面，而且在其不同受体亚型及其转运蛋白的修饰方面。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.