Dopamine modulates episodic memory persistence in old age

J Neurosci. 2012 Oct 10;32(41):14193-204. doi: 10.1523/JNEUROSCI.1278-12.2012.

Abstract

Activation of the hippocampus is required to encode memories for new events (or episodes). Observations from animal studies suggest that, for these memories to persist beyond 4-6 h, a release of dopamine generated by strong hippocampal activation is needed. This predicts that dopaminergic enhancement should improve human episodic memory persistence also for events encoded with weak hippocampal activation. Here, using pharmacological functional MRI (fMRI) in an elderly population in which there is a loss of dopamine neurons as part of normal aging, we show this very effect. The dopamine precursor levodopa led to a dose-dependent (inverted U-shape) persistent episodic memory benefit for images of scenes when tested after 6 h, independent of whether encoding-related hippocampal fMRI activity was weak or strong (U-shaped dose-response relationship). This lasting improvement even for weakly encoded events supports a role for dopamine in human episodic memory consolidation, albeit operating within a narrow dose range.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / drug effects
  • Aging / physiology*
  • Cohort Studies
  • Cross-Over Studies
  • Dopamine / physiology*
  • Dopamine Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • Humans
  • Levodopa / pharmacology
  • Magnetic Resonance Imaging / methods
  • Male
  • Memory, Episodic*
  • Photic Stimulation / methods

Substances

  • Dopamine Agents
  • Levodopa
  • Dopamine