title: Attenuated Tonic and Enhanced Phasic Release of Dopamine in Attention Deficit Hyperactivity Disorder.
abstract: It is unclear whether attention deficit hyperactive disorder (ADHD) is a hypodopaminergic or hyperdopaminergic condition. Different sets of data suggest either hyperactive or hypoactive dopamine system. Since indirect methods used in earlier studies have arrived at contradictory conclusions, we directly measured the tonic and phasic release of dopamine in ADHD volunteers. The tonic release in ADHD and healthy control volunteers was measured and compared using dynamic molecular imaging technique. The phasic release during performance of Eriksen's flanker task was measured in the two groups using single scan dynamic molecular imaging technique. In these experiments volunteers were positioned in a positron emission tomography (PET) camera and administered a dopamine receptor ligand (11)C-raclopride intravenously. After the injection PET data were acquired dynamically while volunteers either stayed still (tonic release experiments) or performed the flanker task (phasic release experiments). PET data were analyzed to measure dynamic changes in ligand binding potential (BP) and other receptor kinetic parameters. The analysis revealed that at rest the ligand BP was significantly higher in the right caudate of ADHD volunteers suggesting reduced tonic release. During task performance significantly lower ligand BP was observed in the same area, indicating increased phasic release. In ADHD tonic release of dopamine is attenuated and the phasic release is enhanced in the right caudate. By characterizing the nature of dysregulated dopamine neurotransmission in ADHD, the results explain earlier findings of reduced or increased dopaminergic activity.
authors.affiliation: Molecular and Functional Imaging Laboratory, Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, United States of America; Neuromodulation Program, University of Minnesota Twin City Campus, Minneapolis, Minnesota, United States of America; Laboratory of Advanced Radiochemistry, University of Minnesota Twin City Campus, Minneapolis, Minnesota, United States of America.
authors.forename: Rajendra D
authors.initials: RD
authors.lastname: Badgaiyan
authors.affiliation: Molecular and Functional Imaging Laboratory, Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Sampada
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Department of Nuclear Medicine, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Munawwar
authors.initials: M
authors.lastname: Sajjad
authors.affiliation: Department of Nuclear Medicine, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: David S
authors.initials: DS
authors.lastname: Wack
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000378:metabolism*; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D057054:Molecular Imaging; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding; D011597:Psychomotor Performance; D011954:Receptors, Dopamine / Q000378:metabolism; D055815:Young Adult
chemical_list: D008024:Ligands; D011954:Receptors, Dopamine; D004298:Dopamine