Age and sex differences in human brain MU opioid receptor binding measured by pet
摘要
Sex and age-related changes in central μ-opioid receptor binding have been suggested in the animal research literature. If similar differences exist in humans, they may explain sex and age effects on normal and pathologic opioid-dependent brain functions. We measured μ-opioid receptor binding in the brains of healthy human subjects with PET and [11C]carfentanil (CFN). Thirty subjects, 12 men and 18 women, aged 19-79 years, were scanned with a GE4096 PET camera after i.v. administration of 20±2 mCi [11C]CFN. Reproductive age women were studied in the follicular phase of their menstrual cycles. Subject positioning in the PET scanner, and region of interest placement in the PET images, were standardized by coaligning the PET imaging plane with CT images of the subject. ANCOVA demonstrated increases in μ binding in neocortical regions and putamen with advancing age (p<0.001). These increases ranged from 36 to 89%from the 3rd decade of life to the 7th decade or older. Statistically significant sex differences were also detected, with higher μ opioid binding in women in neocortical regions, caudate, thalamus, amygdalae and cerebellum, ranging from 8 to 69%during the reproductive years (p<0.05). However, after menopause these sex differences became less prominent, with μ binding approaching levels similar to those of age-matched men in most brain regions. In this regard, ANCOVA detected significant age-by-gender interactions in the amygdalae and thalamus (p<0.05) where postmenopausal women showed binding levels below those of age-matched men. These data imply that both age and gender are important variables to consider in the interpretation of brain function studies in which the opioid system may play a role. Additionally, hormone-mediated alterations in the opioid system during the menopause may be involved in the cognitive and affective changes described during this phase of human aging.