Correlation of striatal dopamine D2/3 receptor availability with GABA level in the anterior cingulate cortex in healthy controls but not in alcohol-dependent subjects and individuals at high risk: A multimodal magnetic resonance spectroscopy and positron emission tomography study

IF 3.1 3区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Addiction Biology Pub Date : 2024-06-20 DOI:10.1111/adb.13424

Gianna Spitta, Tobias Gleich, Annika Rosenthal, Florian Schubert, Semiha Aydin, Andreas Heinz, Ralph Buchert, Jürgen Gallinat

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引用次数: 0

Abstract

Background

The association of impaired dopaminergic neurotransmission with the development and maintenance of alcohol use disorder is well known. More specifically, reduced dopamine D2/3 receptors in the striatum of subjects with alcohol dependence (AD) compared to healthy controls have been found in previous studies. Furthermore, alterations of gamma-aminobutyric acid (GABA) and glutamate (Glu) levels in the anterior cingulate cortex (ACC) of AD subjects have been documented in several studies. However, the interaction between cortical Glu levels and striatal dopamine D2/3 receptors has not been investigated in AD thus far.

Methods

This study investigated dopamine D2/3 receptor availability via 18F-fallypride positron emission tomography (PET) and GABA as well as Glu levels via magnetic resonance spectroscopy (MRS) in 19 detoxified AD subjects, 18 healthy controls (low risk, LR) controls and 19 individuals at high risk (HR) for developing AD, carefully matched for sex, age and smoking status.

Results

We found a significant negative correlation between GABA levels in the ACC and dopamine D2/3 receptor availability in the associative striatum of LR but not in AD or HR individuals. Contrary to our expectations, we did not observe a correlation between Glu concentrations in the ACC and striatal D2/3 receptor availability.

Conclusions

The results may reflect potential regulatory cortical mechanisms on mesolimbic dopamine receptors and their disruption in AD and individuals at high risk, mirroring complex neurotransmitter interactions associated with the pathogenesis of addiction. This is the first study combining 18F-fallypride PET and MRS in AD subjects and individuals at high risk.

Abstract Image

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在健康对照组中，纹状体多巴胺 D2/3 受体的可用性与前扣带回皮层中 GABA 水平的相关性，而在酒精依赖者和高危人群中则不然：多模态磁共振波谱和正电子发射断层扫描研究。

背景：众所周知，多巴胺能神经传递受损与酒精使用障碍的发生和维持有关。更具体地说，以往的研究发现，与健康对照组相比，酒精依赖症（AD）患者纹状体中的多巴胺 D2/3 受体减少。此外，多项研究还发现，酒精依赖症患者前扣带回皮层（ACC）中的γ-氨基丁酸（GABA）和谷氨酸（Glu）水平发生了变化。然而，迄今为止尚未研究过AD患者皮层Glu水平与纹状体多巴胺D2/3受体之间的相互作用：本研究通过18F-呋喃肽正电子发射断层扫描（PET）研究了多巴胺D2/3受体的可用性，并通过磁共振波谱（MRS）研究了19名解毒AD受试者、18名健康对照者（低风险，LR）和19名AD高风险（HR）受试者的GABA和Glu水平：结果：我们发现，ACC 中的 GABA 水平与 LR 人联想纹状体中多巴胺 D2/3 受体的可用性之间存在明显的负相关，但在 AD 或 HR 人中却没有发现。与我们的预期相反，我们没有观察到ACC中Glu浓度与纹状体D2/3受体可用性之间的相关性：这些结果可能反映了大脑皮层对间叶多巴胺受体的潜在调节机制，以及它们在注意力缺陷障碍和高危人群中的破坏，反映了与成瘾发病机制相关的复杂神经递质相互作用。这是首次在AD受试者和高危人群中结合使用18F-芴甲氧甙PET和MRS的研究。

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

Addiction Biology 生物-生化与分子生物学

CiteScore

8.10

自引率

2.90%

发文量

118

审稿时长

6-12 weeks

期刊介绍： Addiction Biology is focused on neuroscience contributions and it aims to advance our understanding of the action of drugs of abuse and addictive processes. Papers are accepted in both animal experimentation or clinical research. The content is geared towards behavioral, molecular, genetic, biochemical, neuro-biological and pharmacology aspects of these fields. Addiction Biology includes peer-reviewed original research reports and reviews. Addiction Biology is published on behalf of the Society for the Study of Addiction to Alcohol and other Drugs (SSA). Members of the Society for the Study of Addiction receive the Journal as part of their annual membership subscription.