title: Dissociable effects of noradrenaline, dopamine, and serotonin uptake blockade on stop task performance in rats.
abstract: BACKGROUND
  The stop-signal paradigm measures the ability to stop a motor response after its execution has been initiated. Impairments in inhibiting inappropriate behavior and prolonged stop-signal reaction times (SSRTs) are characteristic of several psychiatric disorders, most notably attention deficit/hyperactivity disorder. While there is relative consensus regarding the anatomical substrates of behavioral inhibition, the neurochemical imbalance responsible for the deficits in stopping displayed by impulsive individuals is still a matter of debate.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effects of manipulating brain monoamine levels on stop task parameters.
  
  
  METHODS
  Lister-hooded rats were trained on the rodent version of the stop-signal task and administered different monoamine transporter inhibitors: citalopram, which selectively blocks the serotonin transporter; atomoxetine, which selectively blocks the noradrenaline transporter; and GBR-12909, which selectively blocks the dopamine transporter (DAT), and the alpha-2 adrenergic agonist guanfacine.
  
  
  RESULTS
  Atomoxetine speeded SSRT and increased accuracy for go-trials. Citalopram slowed go reaction time and decreased go accuracy at the highest dose (1 mg/kg). GBR-12909 speeded go reaction time and impaired both go and stop accuracy. Guanfacine negatively modulated all principal stop and go measures at the highest dose used (0.3 mg/kg).
  
  
  CONCLUSIONS
  The results suggest that atomoxetine exerts its beneficial effects on SSRT via its action on noradrenaline re-uptake, as the specific DAT blocker GBR-12909 and serotonin reuptake blockade had only minor effects on SSRT. The speeding of the go reaction time by dopamine reuptake blockade is consistent with the hypothesis that the hypothetical stop and go processes are modulated by distinct monoaminergic systems.
authors.affiliation: Department of Experimental Psychology and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge CB23EB, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bari
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Eagle
authors.forename: Adam C
authors.initials: AC
authors.lastname: Mar
authors.forename: Emma S J
authors.initials: ES
authors.lastname: Robinson
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D001522:Behavior, Animal / Q000187:drug effects*; D015283:Citalopram / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016316:Guanfacine / Q000494:pharmacology; D007266:Inhibition, Psychological; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013647:Task Performance and Analysis; D013997:Time Factors
chemical_list: D000069445:Atomoxetine Hydrochloride; D015283:Citalopram; D004298:Dopamine; D016316:Guanfacine; D014179:Neurotransmitter Uptake Inhibitors; D009638:Norepinephrine; D010879:Piperazines; D011437:Propylamines; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C043425:vanoxerine