Glutamate concentration of medial prefrontal cortex is inversely associated with addictive behaviors: a translational study.

IF 5.8 1区 医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2024-10-12 DOI:10.1038/s41398-024-03145-x
Hui Zhou, Tiantian Hong, Xi Chen, Conghui Su, Binyu Teng, Wan Xi, Jean Lud Cadet, Yihong Yang, Fengji Geng, Yuzheng Hu
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Abstract

In both preclinical and clinical settings, dysregulated frontostriatal circuits have been identified as the underlying neural substrates of compulsive seeking/taking behaviors manifested in substance use disorders and behavioral addictions including internet gaming disorder (IGD). However, the neurochemical substrates for these disorders remain elusive. The lack of comprehensive cognitive assessments in animal models has hampered our understanding of neural plasticity in addiction from these models. In this study, combining data from a rat model of compulsive taking/seeking and human participants with various levels of IGD severity, we investigated the relationship between regional glutamate (Glu) concentration and addictive behaviors. We found that Glu levels were significantly lower in the prelimbic cortex (PrL) of rats after 20-days of methamphetamine self-administration (SA), compared to controls. Glu concentration after a punishment phase negatively correlated with acute drug-seeking behavior. In addition, changes in Glu levels from a drug naïve state to compulsive drug taking patterns negatively correlated with drug-seeking during both acute and prolonged abstinence. The human data revealed a significant negative correlation between Glu concentration in the dorsal anterior cingulate cortex (dACC), the human PrL counterpart, and symptoms of IGD. Interestingly, there was a positive correlation between Glu levels in the dACC and self-control, as well as mindful awareness. Further analysis revealed that the dACC Glu concentration mediated the relationship between self-control/mindful awareness and IGD symptoms. These results provide convergent evidence for a protective role of dACC/PrL in addiction, suggesting interventions to enhance dACC glutamatergic functions as a potential strategy for addiction prevention and treatment.

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内侧前额叶皮层的谷氨酸浓度与成瘾行为成反比:一项转化研究。
在临床前和临床环境中,前额纹状体回路失调已被确定为物质使用障碍和行为成瘾(包括网络游戏障碍(IGD))中强迫性寻求/摄取行为的潜在神经基质。然而,这些障碍的神经化学底物仍然难以捉摸。动物模型缺乏全面的认知评估,这阻碍了我们从这些模型中了解成瘾的神经可塑性。在本研究中,我们结合强迫性服用/寻求大鼠模型和不同严重程度 IGD 的人类参与者的数据,研究了区域谷氨酸(Glu)浓度与成瘾行为之间的关系。我们发现,与对照组相比,甲基苯丙胺自我给药 20 天后,大鼠前边缘皮层(PrL)的谷氨酸浓度明显降低。惩罚阶段后的 Glu 浓度与急性觅药行为呈负相关。此外,从药物天真状态到强迫性吸毒模式的 Glu 水平变化与急性和长期戒断期间的觅药行为呈负相关。人类数据显示,与人类PrL相对应的背侧前扣带回皮层(dACC)中的Glu浓度与IGD症状呈显著负相关。有趣的是,dACC 中的 Glu 浓度与自我控制以及心智意识之间存在正相关。进一步的分析表明,dACC Glu浓度在自我控制/正念意识与IGD症状之间起着中介作用。这些结果为dACC/PrL在成瘾中的保护作用提供了聚合证据,表明增强dACC谷氨酸能功能的干预措施是预防和治疗成瘾的一种潜在策略。
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
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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