Evidence that methylphenidate enhances the saliency of a mathematical task by increasing dopamine in the human brain.
OBJECTIVE
Methylphenidate is the most commonly prescribed drug for attention deficit hyperactivity disorder (ADHD), yet its therapeutic mechanisms are poorly understood. The objective of this study was to assess if methylphenidate, by increasing dopamine (neurotransmitter involved in motivation) in brain, would enhance the saliency of an academic task, making it more interesting.


METHODS
Healthy subjects (N=16) underwent positron emission tomography with [(11)C]raclopride (dopamine D(2) receptor radioligand that competes with endogenous dopamine for binding) to assess the effects of oral methylphenidate (20 mg) on extracellular dopamine in the striatum. The authors compared the effects of methylphenidate during an academic task (solving mathematical problems with monetary reinforcement) and a neutral task (passively viewing cards with no remuneration). In parallel, the effects of methylphenidate on the interest that the academic task elicited were also evaluated.


RESULTS
Methylphenidate, when coupled with the mathematical task, significantly increased extracellular dopamine, but this did not occur when coupled with the neutral task. The mathematical task did not increase dopamine when coupled with placebo. Subjective reports about interest and motivation in the mathematical task were greater with methylphenidate than with placebo and were associated with dopamine increases.


CONCLUSIONS
The significant association between methylphenidate-induced dopamine increases and the interest and motivation for the task confirms the prediction that methylphenidate enhances the saliency of an event by increasing dopamine. The enhanced interest for the task could increase attention and improve performance and could be one of the mechanisms underlying methylphenidate's therapeutic effects. These findings support educational strategies that make schoolwork more interesting as nonpharmacological interventions to treat ADHD.
Volkow
Nora D
ND
Medical and Chemistry Departments, Brookhaven National Laboratory, Upton, NY, USA.
Wang
Gene-Jack
GJ
Fowler
Joanna S
JS
Telang
Frank
F
Maynard
Laurence
L
Logan
Jean
J
Gatley
Samuel J
SJ
Pappas
Naomi
N
Wong
Christopher
C
Vaska
Paul
P
Zhu
Wei
W
Swanson
James M
JM
D000328:Adult; D001288:Attention / Q000187:drug effects / Q000502:physiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000523:psychology; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D008297:Male; D008433:Mathematics; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors; D008774:Methylphenidate / Q000494:pharmacology*; D009042:Motivation; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D010919:Placebos; D011340:Problem Solving / Q000187:drug effects* / Q000502:physiology; D020891:Raclopride; D012201:Reward; D013647:Task Performance and Analysis; D014055:Tomography, Emission-Computed
D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010919:Placebos; D008774:Methylphenidate; D020891:Raclopride; D004298:Dopamine