Global Increase in Cortical Opioid Binding Potential with Aging: In Vivo Quantification with 11C diprenorphine PET

Abstract

Background:Recent studies using positron emission tomography (PET) have shown an increase of μ‐opioid receptors with aging in the human brain. However, its physiological role and relationship between the other subtypes of opioid receptors is still obscure. We used a non‐selective radiotracer [11C]diprenorphine and PET to estimate the effects of aging on brain opioid binding. Methods:Seventeen normal male subjects were studied. Their ages ranged from 27 to 65 years (mean; 46 years). The data was analysed with global and regional opioid activities on images reflecting binding potential (Bmax/Kd) using statistical parametric mapping (SPM). Results:The main effect of age was shown in the global opioid binding potential (p=0.046). A post‐hoc test revealed that the binding potentials began to increase abruptly in those aged 40 and above. SPM found that the binding activity of brain opioid receptors significantly increased with age throughout the cerebral cortex except in the primary visual and sensory‐motor cortices where little specific binding occurs. There were no age‐related changes in subcortical structures except for a part of the putamen. Conclusion:The increase of opioid binding activities with aging probably depends on the density of μ‐opioid receptors, not K‐ nor δ‐ opioid receptors in association cortices. The detailed distribution shown by SPM suggests that this phenomenon may not be due to compensatory up‐regulation by the decrease in the endogenous opioid. The Increase of cortical opioid binding may contribute to the pathophysiology of depression and high risk of suicide attempts with advancing age.