Methylphenidate and atomoxetine increase histamine release in rat prefrontal cortex.

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.