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

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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-[18F]Fluoro-d-glucose ([18F]FDG) microPET imaging was performed, and statistical parametric mapping (SPM) was used for image analysis. Glucose transporter 3 (Glut-3), dopamine D2 receptor (D2R), 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, D2R, 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 D2R or μ-OR in CC, rRSD, and rVP.

Conclusions

[18F]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.

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Acknowledgements

This work was partly sponsored by the National Natural Science Foundation of China (81301243,81425015), the Natural Science Foundation of Zhejiang Province (LY17H180004), the Research Fund for the Doctoral Program of Higher Education of China (20120101120031), the grants from the Health Bureau of Zhejiang Province (2014KYA095, WKJ2013-2-016), and supported by Zhejiang University K. P. Chao’s High Technology Development.

Author information

Author notes

  1. Qing Chen, Haifeng Hou and Jin Feng contributed equally to this work.

Authors and Affiliations

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

    Qing Chen, Haifeng Hou, Jin Feng, Xiaohui Zhang, Yao Chen, Jing Wang, Jianfeng Ji, Xiao He, Hao Wu & Hong Zhang

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

    Qing Chen, Haifeng Hou, Jin Feng, Xiaohui Zhang, Yao Chen, Jing Wang, Jianfeng Ji, Xiao He, Hao Wu & Hong Zhang

  3. Institute of Nuclear Medicine and Molecular Imaging, Zhejiang University, Hangzhou, 310009, China

    Qing Chen, Haifeng Hou, Jin Feng, Xiaohui Zhang, Yao Chen, Jing Wang, Jianfeng Ji, Xiao He, Hao Wu & Hong Zhang

  4. Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009, China

    Qing Chen, Haifeng Hou, Jin Feng, Xiaohui Zhang, Yao Chen, Jing Wang, Jianfeng Ji, Xiao He, Hao Wu & Hong Zhang

Authors
  1. Qing Chen
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  2. Haifeng Hou
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  3. Jin Feng
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  5. Yao Chen
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  7. Jianfeng Ji
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  8. Xiao He
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  9. Hao Wu
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  10. Hong Zhang
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Corresponding authors

Correspondence to Haifeng Hou or Hong Zhang.

Ethics declarations

All animal studies were approved by the Zhejiang University Ethics Committee for Animal Experiments (Protocol No. ZJU2015-069-02).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Chen, Q., Hou, H., Feng, J. et al. PET Imaging Reveals Brain Metabolic Changes in Adolescent Rats Following Chronic Escalating Morphine Administration. Mol Imaging Biol 20, 993–1000 (2018). https://doi.org/10.1007/s11307-018-1188-9

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  • DOI: https://doi.org/10.1007/s11307-018-1188-9

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