title: Modulation of high impulsivity and attentional performance in rats by selective direct and indirect dopaminergic and noradrenergic receptor agonists.
abstract: BACKGROUND
  Impulsivity is associated with a number of psychiatric disorders, most notably attention deficit/hyperactivity disorder (ADHD). Drugs that augment catecholamine function (e.g. methylphenidate and the selective noradrenaline reuptake inhibitor atomoxetine) have clinical efficacy in ADHD, but their precise mechanism of action is unclear.
  
  
  OBJECTIVE
  The objective of this study is to investigate the relative contribution of dopamine (DA) and noradrenaline (NA) to the therapeutic effects of clinically effective drugs in ADHD using rats selected for high impulsivity on the five-choice serial reaction time task (5CSRTT).
  
  
  METHODS
  We examined the effects of direct and indirect DA and NA receptor agonists and selective DA and NA reuptake inhibitors in rats showing high and low levels of impulsivity on the 5CSRTT (designated high impulsive 'HI' and low impulsive 'LI', respectively). Drugs were administered by systemic injection in a randomized, counterbalanced manner.
  
  
  RESULTS
  Low doses of quinpirole (a D2/D3 agonist) and sumanirole (a D2 agonist) selectively reduced impulsivity on the 5CSRTT, whilst higher doses resulted in increased omissions and slower response latencies. The NA reuptake inhibitor, atomoxetine, and the alpha-2 adrenoreceptor agonist, guanfacine, dose dependently decreased premature responding. The dopaminergic reuptake inhibitor GBR-12909 increased impulsivity, whereas the nonselective DA and NA reuptake inhibitor methylphenidate had no significant effect on impulsive responses in HI and LI rats.
  
  
  CONCLUSIONS
  These findings indicate that high impulsivity can be ameliorated in rats by drugs that mimic the effects of DA and NA, just as in ADHD, and that activation of D2/3 receptors selectively decreases high impulsivity on the 5CSRTT.
authors.affiliation: Behavioural and Clinical Neuroscience Institute and Department of Experimental Psychology, University of Cambridge, Downing St, Cambridge, CB2 3EB, UK.
authors.forename: Anushka B P
authors.initials: AB
authors.lastname: Fernando
authors.forename: Daina
authors.initials: D
authors.lastname: Economidou
authors.forename: David E
authors.initials: DE
authors.lastname: Theobald
authors.forename: Mu-Fa
authors.initials: MF
authors.lastname: Zou
authors.forename: Amy H
authors.initials: AH
authors.lastname: Newman
authors.forename: Marcia
authors.initials: M
authors.lastname: Spoelder
authors.forename: Daniele
authors.initials: D
authors.lastname: Caprioli
authors.forename: Margarita
authors.initials: M
authors.lastname: Moreno
authors.forename: Lucia
authors.initials: L
authors.lastname: Hipólito
authors.forename: Albert T
authors.initials: AT
authors.lastname: Aspinall
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Dalley
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D021461:Animals, Outbred Strains; D000069445:Atomoxetine Hydrochloride; D001288:Attention / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D002755:Choice Behavior / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D016316:Guanfacine / Q000494:pharmacology / Q000627:therapeutic use; D007175:Impulsive Behavior / Q000188:drug therapy*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011437:Propylamines / Q000494:pharmacology / Q000627:therapeutic use; D019257:Quinpirole / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D012691:Serial Learning / Q000187:drug effects
chemical_list: D000322:Adrenergic Agonists; D001562:Benzimidazoles; D018491:Dopamine Agonists; D010879:Piperazines; D011437:Propylamines; D008774:Methylphenidate; D019257:Quinpirole; C108539:U 95666E; D016316:Guanfacine; D000069445:Atomoxetine Hydrochloride; C043425:vanoxerine