Gender and age influences on human brain mu-opioid receptor binding measured by PET

Objective: Both age and gender are being increasingly recognized as importa nt factors influencing CNS structure and function. However, there are relat ively few data on actual neurochemical differences between the sexes in hum an subjects or on their interaction with age. One of the central neurotrans mitter systems for which sex differences have been suggested by animal mode ls and clinical human data is the opioid. In this study the authors examine d age- and gender-associated variations in mu-opioid receptor binding with positron emission tomography (PET). Method: Healthy human subjects were stu died with PET and the radiotracer [C-11]carfentanil, a selective mu-opioid agonist. Two separate subject groups were examined: one group of 24 men and 12 women was studied in a retrospective analysis of data, and a second gro up of 12 men and 18 women was recruited prospectively and studied with a hi gher-resolution scanner. Results: Mu-opioid receptor binding potential (B-m ax/K-d) was found to increase with age in neocortical areas and the putamen . Sex differences, with higher mu-opioid binding in women, were observed in a number of cortical and subcortical areas. Gender-by-age interactions wer e observed in the thalamus and the amygdala; in vivo mu-opioid binding decl ined in postmenopausal women to levels below those of men. Conclusions: The se data imply that both age and gender are important variables to consider in the interpretation of investigations of human function in which the opio id system plays a role. Also, women's reproductive status (reproductive age versus postmenopausal) may influence the function of CNS opioid systems.