Dopamine vs noradrenaline: inverted-U effects and ADHD theories.
The aim of the present study was to review the dopamine theory of attention-deficit-hyperactivity disorder (ADHD), in light of recent use of noradrenergic therapies. A historical review of pharmacological theories of ADHD was conducted, including inverted-U, spatial working memory and neural circuit aspects. Pharmacological advances, including animal and human studies of dopaminergic and noradrenergic mechanisms at the prefrontal cortex (PFC), indicate that alpha-2A adrenoreceptor stimulation results in increased dendritic firing during delay periods for preferred directions, while moderate levels of D1 receptor stimulation result in reduction of delay-related firing to non-preferred directions, allowing representational control in the PFC. Recent studies of the COMT val/met gene and stimulant medication response may help explain variation in inverted-U responses in individuals. Further studies utilizing delay-related firing paradigms should be useful in the investigation of attentional syndromes, and responses to newer pharmacological treatments.
Levy
Florence
F
School of Psychiatry, University of New South Wales,, Prince of Wales Hospital, Randwick, New South Wales, Australia. f.levy@unsw.edu.au
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000483:Alleles; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000235:genetics; D004298:Dopamine / Q000378:metabolism*; D016316:Guanfacine / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008570:Memory, Short-Term / Q000187:drug effects; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011437:Propylamines / Q000494:pharmacology / Q000627:therapeutic use*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D050638:Receptors, Dopamine D4 / Q000235:genetics; D013028:Space Perception / Q000187:drug effects; D013788:Thalamus / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D000316:Adrenergic alpha-Agonists; C493599:DRD4 protein, human; D011437:Propylamines; D018341:Receptors, Adrenergic, alpha-2; D050638:Receptors, Dopamine D4; D016316:Guanfacine; D000069445:Atomoxetine Hydrochloride; D002394:Catechol O-Methyltransferase; D004298:Dopamine; D009638:Norepinephrine