title: Stimulant side effects: prefrontal/basal ganglia circuit control at dopamine D1/D2 receptors.
abstract: BACKGROUND
  While side effects of stimulant medication used to treat children for attention deficit hyperactivity disorder have been clinically described as mild but variable, there is little or no research or understanding of biological mechanisms involved.
  
  
  METHODS
  The present short review extends the 'tonic-phasic' dopamine hypothesis in terms of prefrontal and subcortical dopamine receptor (D1/D2) imbalance.
  
  
  RESULTS
  The minor allele of the dopamine D1 receptor predicts the 'zombie-like' motor side effect clinically described in some children treated with stimulant medications.
  
  
  CONCLUSIONS
  Stimulant side effects may be best understood as reflecting imbalance in parallel cortico-thalamic-striatal circuits, and motor side effects as a result of prefrontal D1/D2 imbalance allowing greater motor inhibitory effects at subcortical D2 receptors. This is a variation of the 'tonic-phasic' hypothesis, which takes D1 allelic variation into account.
authors.affiliation: School of Psychiatry, Prince of Wales Hospital and University of New South Wales, Sydney, NSW, Australia.
authors.forename: Florence
authors.initials: F
authors.lastname: Levy
authors.forename: Mark R
authors.initials: MR
authors.lastname: Dadds
mesh_terms: D000483:Alleles; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D002648:Child; D006801:Humans; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; C583260:DRD1 protein, human; C581293:DRD2 protein, human; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2
keywords: ADHD; COMT; D1 receptor; side effects; stimulants