Methylphenidate and atomoxetine increase histamine release in rat prefrontal cortex

Eur J Pharmacol. 2007 Mar 8;558(1-3):96-7. doi: 10.1016/j.ejphar.2006.11.048. Epub 2006 Dec 1.


Using microdialysis in rat prefrontal cortex, we found that 1 mg/kg of the stimulant methylphenidate and the non-stimulant atomoxetine, two widely used treatments for Attention Deficit/Hyperactivity Disorder (ADHD), produce robust increases in the extracellular levels of histamine, which plays a key role in attention, learning and memory. While the clinical response to ADHD drugs is typically attributed to modulation of norepinephrine and dopamine, this finding suggests enhanced histamine release may contribute to their efficacy as ADHD treatments.

MeSH terms

  • Animals
  • Atomoxetine Hydrochloride
  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Histamine Release / drug effects*
  • Male
  • Methylphenidate / pharmacology*
  • Methylphenidate / therapeutic use
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Propylamines / pharmacology*
  • Propylamines / therapeutic use
  • Rats
  • Rats, Sprague-Dawley


  • Propylamines
  • Methylphenidate
  • Atomoxetine Hydrochloride