title: Noradrenergic versus dopaminergic modulation of impulsivity, attention and monitoring behaviour in rats performing the stop-signal task: possible relevance to ADHD.
abstract: BACKGROUND
  Deficient response inhibition is a prominent feature of many pathological conditions characterised by impulsive and compulsive behaviour. Clinically effective doses of catecholamine reuptake inhibitors are able to improve such inhibitory deficits as measured by the stop-signal task (SST) in humans and other animals. However, the precise therapeutic mode of action of these compounds in terms of their relative effects on dopamine (DA) and noradrenaline (NA) systems in prefrontal cortical and striatal regions mediating attention and cognitive control remains unclear.
  
  
  OBJECTIVE
  We sought to fractionate the effects of global catecholaminergic manipulations on SST performance by using receptor-specific compounds for NA or DA. The results are described in terms of the effects of modulating specific receptor subtypes on various behavioural measures such as response inhibition, perseveration, sustained attention, error monitoring and motivation.
  
  
  RESULTS
  Blockade of α2-adrenoceptors improved sustained attention and response inhibition, whereas α1 and β1/2 adrenergic receptor antagonists disrupted go performance and sustained attention, respectively. No relevant effects were obtained after targeting DA D1, D2 or D4 receptors, while both a D3 receptor agonist and antagonist improved post-error slowing and compulsive nose-poke behaviour, though generally impairing other task measures.
  
  
  CONCLUSIONS
  Our results suggest that the use of specific pharmacological agents targeting α2 and β noradrenergic receptors may improve existing treatments for attentional deficits and impulsivity, whereas DA D3 receptors may modulate error monitoring and perseverative behaviour.
authors.affiliation: Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, CB2 3EB, UK, andbari@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Bari
authors.forename: T W
authors.initials: TW
authors.lastname: Robbins
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D007175:Impulsive Behavior / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009042:Motivation; D009638:Norepinephrine / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000187:drug effects / Q000378:metabolism
chemical_list: D018341:Receptors, Adrenergic, alpha-2; D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D050637:Receptors, Dopamine D3; D004298:Dopamine; D009638:Norepinephrine