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Published on: August 11, 2021
Methylphenidate and atomoxetine increase histamine release in rat prefrontal cortex
Weldon E Horner1, David E Johnson, Anne W Schmidt
1Department of Neuroscience, MS 8220-4159, Pfizer Global Research and Development, Groton, CT 06340 USA.
Attention Deficit/Hyperactivity Disorder (ADHD) medications, methylphenidate and atomoxetine, significantly increase histamine levels in the brain. This suggests histamine release may be crucial for ADHD treatment efficacy.
Area of Science:
- Neuroscience
- Pharmacology
- Neurochemistry
Background:
- Attention Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder.
- Current ADHD treatments primarily target norepinephrine and dopamine pathways.
- Histamine is recognized for its role in cognitive functions like attention, learning, and memory.
Purpose of the Study:
- To investigate the effects of ADHD medications on histamine levels in the rat prefrontal cortex.
- To explore potential novel mechanisms of action for ADHD treatments.
Main Methods:
- Microdialysis was employed in the prefrontal cortex of rats.
- The extracellular levels of histamine were measured following administration of methylphenidate and atomoxetine.
Main Results:
- Both the stimulant methylphenidate and the non-stimulant atomoxetine caused significant increases in extracellular histamine levels.
- These increases were robust and observed in the prefrontal cortex.
Conclusions:
- The findings suggest that enhanced histamine release is a common effect of both stimulant and non-stimulant ADHD medications.
- This histamine modulation may represent a significant, previously underappreciated, mechanism contributing to the therapeutic efficacy of ADHD treatments.
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