Enhanced phasic and attenuated tonic release of striatal dopamine in attention deficit hyperactivity disorder

Objectives Studies have reported either hypo or hyperactive dopaminergic activity in attention deficit hyperactivity disorder (ADHD). The disagreement could be due to measurement of either tonic or phasic release of dopamine. Studies that have measured the tonic release have found reduced activity and hyperactivity is observed in studies that have measured the phasic release. We therefore hypothesized that in ADHD the tonic release is reduced and phasic release is enhanced. This hypothesis was examined using a dynamic molecular imaging technique (1-7).

Methods We measured tonic and phasic release of striatal dopamine in ADHD patients (n=20) and healthy control volunteers (n=20). The phasic release was measured during performance of Eriksen’s flanker task. Volunteers were positioned in a PET camera and administered an IV bolus of a dopamine receptor ligand (11C-raclopride). Thereafter, they were asked to perform the task under a control (congruent) and a test (incongruent) condition. To measure the tonic release, volunteers were asked to stay still in the camera after the ligand administration. In all experiments PET data were acquired dynamically at 30 sec intervals and data analyzed using modified simplified reference tissue models (8, 9).

Results We observed higher (3.05±0.85) ligand binding potential in ADHD patients in comparison with healthy volunteers (2.68±0.69) at rest. It indicates attenuated tonic pool in patients. During task performance dopamine release was detected bilaterally in the caudate and putamen of ADHD volunteers while it was found only in the left caudate and bilateral putamen in healthy subjects. Additionally, after task initiation there was greater reduction in the ligand BP in the ADHD group (0.27±0.40), as compared to that in healthy group (0.01±0.27). These data indicate increased phasic release in ADHD during task performance.

Conclusions In ADHD tonic release of dopamine is attenuated and there is compensatory enhancement of phasic release.

Research Support NIH (1R01NS073884;1R21MH073624) and VA (CX000479; CX000780) grants