Cognitive effects of methylphenidate and levodopa in healthy volunteers

Eur Neuropsychopharmacol. 2014 Feb;24(2):200-6. doi: 10.1016/j.euroneuro.2013.09.009. Epub 2013 Oct 4.


Our previous study showed enhanced declarative memory consolidation after acute methylphenidate (MPH) administration. The primary aim of the current study was to investigate the duration of this effect. Secondary, the dopaminergic contribution of MPH effects, the electrophysiological correlates of declarative memory, and the specificity of memory enhancing effects of MPH to declarative memory were assessed. Effects of 40 mg of MPH on memory performance were compared to 100mg of levodopa (LEV) in a placebo-controlled crossover study with 30 healthy volunteers. Memory performance testing included a word learning test, the Sternberg memory scanning task, a paired associates learning task, and a spatial working memory task. During the word learning test, event-related brain potentials (ERPs) were measured. MPH failed to enhance retention of words at a 30 min delay, but it improved 24 h delayed memory recall relative to PLA and LEV. Furthermore, during encoding, the P3b and P600 ERP latencies were prolonged and the P600 amplitude was larger after LEV compared to PLA and MPH. MPH speeded response times on the Sternberg Memory Scanning task and improved performance on the Paired Associates Learning task, relative to LEV, but not PLA. Performance on the Spatial working memory task was not affected by the treatments. These findings suggest that MPH and LEV might have opposite effects on memory.

Keywords: Dopamine; Event-related potentials; Levodopa; Memory; Methylphenidate.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Association Learning / drug effects
  • Association Learning / physiology
  • Brain / drug effects*
  • Brain / physiology
  • Cross-Over Studies
  • Dopamine Agents / pharmacology*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Double-Blind Method
  • Evoked Potentials / drug effects
  • Female
  • Healthy Volunteers
  • Humans
  • Levodopa / pharmacology*
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • Memory, Short-Term / drug effects
  • Memory, Short-Term / physiology
  • Mental Recall / drug effects
  • Mental Recall / physiology
  • Methylphenidate / pharmacology*
  • Recognition, Psychology / drug effects
  • Recognition, Psychology / physiology
  • Space Perception / drug effects
  • Space Perception / physiology
  • Young Adult


  • Dopamine Agents
  • Dopamine Uptake Inhibitors
  • Methylphenidate
  • Levodopa