title: Blockade of noradrenaline re-uptake sites improves accuracy and impulse control in rats performing a five-choice serial reaction time tasks.
abstract: BACKGROUND
  Atomoxetine, reboxetine and methylphenidate all act at the noradrenaline transporter (NAT) and atomoxetine and methylphenidate are licensed for the treatment of ADHD. The five-choice serial reaction time task (5CSRTT) provides a valid model to study attention and impulsivity in rodents. Studies using this task have largely failed to demonstrate improvements in attention with atomoxetine and methylphenidate and reboxetine has not been investigated previously.
  
  
  OBJECTIVE
  The present study used modifications to the standard rat 5CSRTT and demonstrated that blockade of NAT improves attention and reduces premature responding.
  
  
  METHODS
  Rats were trained in a fixed inter-trial interval (ITI), 5CSRTT then tested at baseline and under conditions to acutely challenge attention and/or impulse control following vehicle or atomoxetine (0.3 mg/kg, i.p.).
  
  
  RESULTS
  Atomoxetine (0.3 mg/kg, i.p.) significantly improved impulse control under all conditions (p < 0.05) but had no significant effects on accuracy. To increase the attentional demands of the task, rats were re-baselined in a non-paced, variable ITI task where presentations of the stimuli were unpredictable. In the VITI task, atomoxetine (0.0-0.3 mg/kg, i.p.) induced a dose-dependent improvement in accuracy (p < 0.05) and reduction in premature responses (p < 0.05). Reboxetine (0.0-1.0 mg/kg, i.p.) and methylphenidate (1-10 mg/kg, p.o.) did not significantly improve accuracy in the whole population but median split analysis revealed a significant improvement with both drugs, as well as atomoxetine, in the poor performing animals (p < 0.05).
  
  
  CONCLUSIONS
  These data suggest that blockade of noradrenaline re-uptake sites is an important target in terms of enhancing both attention and impulse control.
authors.affiliation: School of Physiology and Pharmacology, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK. pmesjr@bris.ac.uk
authors.forename: Emma S J
authors.initials: ES
authors.lastname: Robinson
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D021461:Animals, Outbred Strains; D000069445:Atomoxetine Hydrochloride; D001288:Attention / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007175:Impulsive Behavior / Q000188:drug therapy*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology / Q000627:therapeutic use; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D011437:Propylamines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011930:Reaction Time / Q000187:drug effects*; D000077593:Reboxetine; D012691:Serial Learning / Q000187:drug effects*; D013997:Time Factors
chemical_list: D018759:Adrenergic Uptake Inhibitors; D009025:Morpholines; D011437:Propylamines; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride; D000077593:Reboxetine