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正电子发射断层扫描成像显示慢性递增吗啡给药后青春期大鼠大脑代谢变化。

PET Imaging Reveals Brain Metabolic Changes in Adolescent Rats Following Chronic Escalating Morphine Administration.

机构信息

Department of Nuclear Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.

Zhejiang University Medical PET Centre, Zhejiang University, Hangzhou, 310009, China.

出版信息

Mol Imaging Biol. 2018 Dec;20(6):993-1000. doi: 10.1007/s11307-018-1188-9.

Abstract

PURPOSE

Non-medical use of prescription opioids, especially among adolescents, has been substantially increased in recent years. However, the neuromechanism remains largely unexplored. In the present study, we aimed to investigate the brain metabolic changes in adolescent rats following chronic escalating morphine administration using positron emission tomography (PET).

PROCEDURES

2-Deoxy-2-[F]Fluoro-D-glucose ([F]FDG) microPET imaging was performed, and statistical parametric mapping (SPM) was used for image analysis. Glucose transporter 3 (Glut-3), dopamine D receptor (DR), and Mμ-opioid receptor (μ-OR) were used for immunostaining analysis.

RESULTS

Cerebral glucose metabolism was increased in the corpus callosum (CC) and right retrosplenial dysgranular cortex (rRSD), while it was decreased in the right ventral pallidum (rVP). The expressions of Glut-3, DR, and μ-OR were increased in CC and rRSD, while they were decreased in rVP. Furthermore, glucose metabolism and Glut-3 expression were positively correlated with the expressions of DR or μ-OR in CC, rRSD, and rVP.

CONCLUSIONS

[F]FDG microPET brain imaging study in combination with immunohistological investigation revealed that CC, rRSD, and rVP were specifically involved in opioid dependence in adolescents. Our findings provided valuable insights into the neuromechanism of adolescent addiction of prescription opioids and might have important implications for the development of prevention and intervention approaches.

摘要

目的

近年来,非医疗用途的处方类阿片类药物(尤其是在青少年中)的使用大幅增加。然而,其神经机制在很大程度上仍未得到探索。本研究旨在通过正电子发射断层扫描(PET)研究慢性递增吗啡给药后青少年大鼠的大脑代谢变化。

方法

进行 2-脱氧-2-[F]氟-D-葡萄糖([F]FDG)microPET 成像,并使用统计参数映射(SPM)进行图像分析。使用葡萄糖转运蛋白 3(Glut-3)、多巴胺 D 受体(DR)和 Mμ-阿片受体(μ-OR)进行免疫染色分析。

结果

大脑葡萄糖代谢在胼胝体(CC)和右侧后扣带回颗粒区(rRSD)增加,而在右侧腹侧苍白球(rVP)减少。Glut-3、DR 和 μ-OR 的表达在 CC 和 rRSD 中增加,而在 rVP 中减少。此外,CC、rRSD 和 rVP 中的葡萄糖代谢和 Glut-3 表达与 DR 或 μ-OR 的表达呈正相关。

结论

[F]FDG microPET 脑成像研究结合免疫组织化学研究表明,CC、rRSD 和 rVP 特异性参与了青少年对处方类阿片的依赖。我们的研究结果为处方类阿片成瘾的青少年神经机制提供了有价值的见解,可能对预防和干预方法的发展具有重要意义。

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