Age-related differences in striatal dopamine D1 receptors mediate subjective drug effects

Using PET imaging, we collected measures of D1Rs and D2Rs and estimates of MP-induced dopamine increases to study the effect of age on the subjective experience of MP in healthy adults. Periodically throughout the sessions, participants were asked to rate, on a scale of 1 to 10, several questions about their subjective experience of drug reward in response to MP. We characterized associations among D1R, D2R, and dopamine increases with age and subjective drug effects at the voxel level and at the region-of-interest (accumbens and dorsal striatum) level. In sum, declines in accumbens D1R availability (but not D2R availability or MP-induced dopamine increases) may explain why people feel stimulant drug effects less strongly as they age, providing a possible neural mechanism for the lower prevalence of stimulant use disorders in elderly individuals compared with that in young adults (5).