Dopamine D(1) receptors and age differences in brain activation during working memory

Neurobiol Aging. 2011 Oct;32(10):1849-56. doi: 10.1016/j.neurobiolaging.2009.10.018. Epub 2009 Dec 4.


In an fMRI study, 20 younger and 20 healthy older adults were scanned while performing a spatial working-memory task under two levels of load. On a separate occasion, the same subjects underwent PET measurements using the radioligand [(11)C] SCH23390 to determine dopamine D(1) receptor binding potential (BP) in caudate nucleus and dorsolateral prefrontal cortex (DLPFC). The fMRI study revealed a significant load modulation of brain activity (higher load>lower load) in frontal and parietal regions for younger, but not older, adults. The PET measurements showed marked age-related reductions of D(1) BP in caudate and DLPFC. Statistical control of caudate and DLPFC D(1) binding eliminated the age-related reduction in load-dependent BOLD signal in left frontal cortex, and attenuated greatly the reduction in right frontal and left parietal cortex. These findings suggest that age-related alterations in dopaminergic neurotransmission may contribute to underrecruitment of task-relevant brain regions during working-memory performance in old age.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / drug effects
  • Aging / physiology*
  • Benzazepines / pharmacokinetics
  • Brain / blood supply
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / metabolism*
  • Brain Mapping
  • Carbon Isotopes / pharmacokinetics
  • Dopamine Antagonists / pharmacokinetics
  • Female
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Magnetic Resonance Imaging / methods
  • Male
  • Memory, Short-Term / drug effects
  • Memory, Short-Term / physiology*
  • Neuropsychological Tests
  • Oxygen / blood
  • Positron-Emission Tomography
  • Receptors, Dopamine D1 / metabolism*
  • Young Adult


  • Benzazepines
  • Carbon Isotopes
  • Dopamine Antagonists
  • Receptors, Dopamine D1
  • SCH 23390
  • Oxygen