Haloperidol impairs learning and error-related negativity in humans

J Cogn Neurosci. Jul-Aug 2004;16(6):1098-112. doi: 10.1162/0898929041502779.


Humans are able to monitor their actions for behavioral conflicts and performance errors. Growing evidence suggests that the error-related negativity (ERN) of the event-related cortical brain potential (ERP) may index the functioning of this response monitoring system and that the ERN may depend on dopaminergic mechanisms. We examined the role of dopamine in ERN and behavioral indices of learning by administering either 3 mg of the dopamine antagonist (DA) haloperidol (n = 17); 25 mg of diphenhydramine (n = 16), which has a similar CNS profile but without DA properties; or placebo (n = 18) in a randomized, double-blind manner to healthy volunteers. Three hours after drug administration, participants performed a go/no-go Continuous Performance Task, the Eriksen Flanker Task, and a learning-dependent Time Estimation Task. Haloperidol significantly attenuated ERN amplitudes recorded during the flanker task, impaired learning of time intervals, and tended to cause more errors of commission, compared to placebo, which did not significantly differ from diphenhydramine. Drugs had no significant effects on the stimulus-locked P1 and N2 ERPs or on behavioral response latencies, but tended to affect post-error reaction time (RT) latencies in opposite ways (haloperidol decreased and diphenhydramine increased RTs). These findings support the hypothesis that the DA system is involved in learning and the generation of the ERN.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analysis of Variance
  • Brain Mapping / methods
  • Diphenhydramine / pharmacology
  • Dopamine Antagonists / adverse effects*
  • Dopamine Antagonists / pharmacology
  • Double-Blind Method
  • Drug Interactions
  • Electroencephalography / methods
  • Evoked Potentials / drug effects*
  • Female
  • Haloperidol / adverse effects*
  • Haloperidol / pharmacology
  • Humans
  • Hypnotics and Sedatives / pharmacology
  • Learning Disabilities / chemically induced*
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Psychomotor Performance / drug effects
  • Reaction Time / drug effects
  • Time Factors
  • Time Perception / drug effects


  • Dopamine Antagonists
  • Hypnotics and Sedatives
  • Diphenhydramine
  • Haloperidol