A serum-based insight into dopaminergic dysregulation and mesocorticolimbic network imbalance in methamphetamine addiction

Abstract Background Chronic methamphetamine (MA) use leads to dopaminergic system dysfunction, particularly through the downregulation of dopamine D2 receptors (D2Rs). Neuroimaging studies have consistently shown altered functional connectivity within the mesocorticolimbic system in individuals with MA addiction. This study aims to examine the association between serum D2R protein levels and functional connectivity within the reward network in cognitively impaired methamphetamine addicts. Forty-six MA addicts and forty-four healthy controls (HCs) were studied. All participants were examined clinically. Blood samples were collected to quantify serum D2R protein levels using enzyme-linked immunosorbent assay. Resting-state brain activity was assessed using quantitative electroencephalography (qEEG), with a focus on functional connectivity between the amygdala and orbitofrontal cortex (Brodmann area 11). Results Compared to HCs, MA addicts have lower serum D2R levels ( p < 0.001) and reduced synchronization between the right orbitofrontal cortex (Brodmann area 11) and the amygdala through functional connectivity analysis ( p = 0.016). Moreover, serum D2R levels were negatively correlated with right amygdala-to-BA 11 coherence parameters ( r = -0.240; p < 0.05). Conclusion MA addiction is associated with decreased serum D2R protein levels and disrupted functional connectivity between key regions of the reward network, specifically the amygdala and orbitofrontal cortex. Peripheral D2R may serve as a potential biomarker for dopaminergic dysfunction in addiction.