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

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).

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.

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.

[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.