Sub-optimal performance in the 5-choice serial reaction time task in rats was sensitive to methylphenidate, atomoxetine and d-amphetamine, but unaffected by the COMT inhibitor tolcapone

Neurosci Res. 2011 Jan;69(1):41-50. doi: 10.1016/j.neures.2010.10.001. Epub 2010 Oct 8.


Prefrontal cortical dopamine (DA) and norepinephrine (NE) are implicated in multiple aspects of cognitive function assessed via the 5-choice serial reaction time task (5-CSRTT) in rodents. The present studies assessed the effects of the NE reuptake inhibitor atomoxetine (0.5-2.0 mg/kg), the mixed DA/NE reuptake inhibitor methylphenidate (0.1-2.0 mg/kg), the catecholamine releaser D-amphetamine (0.1-1.0 mg/kg) and the catecholamine-o-methyl-transferase (COMT) inhibitor tolcapone (3.0-30.0 mg/kg) in rats that exhibited sub-optimal performance (reduced accuracy: <70% correct) in the 5-CSRTT. Increased ITI durations were associated with increased premature responding. Decreased ITI durations resulted in increased percent omissions, increased perseverative responses and increased response latencies, but had no effects on magazine latencies or percent correct. Atomoxetine decreased premature responding at prolonged ITI durations and methylphenidate decreased percent omissions at low doses (0.1 and 0.5 mg/kg). By contrast, D-amphetamine increased premature and perseverative responding in a dose-dependent manner (0.3-1.0 mg/kg). Finally, tolcapone had no effects on sub-optimal performance in the variable ITI 5-CSRTT. These results suggest minimal potential of tolcapone as a therapeutic agent for ADHD and implicate cortical NE, not DA, in impulsive action.

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Animals
  • Atomoxetine Hydrochloride
  • Attention / drug effects*
  • Attention / physiology
  • Benzophenones / pharmacology*
  • Catechol O-Methyltransferase Inhibitors
  • Central Nervous System Stimulants / pharmacology
  • Choice Behavior / drug effects*
  • Choice Behavior / physiology
  • Dextroamphetamine / pharmacology*
  • Dopamine / pharmacology
  • Dopamine Uptake Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Impulsive Behavior / drug therapy
  • Male
  • Methylphenidate / pharmacology*
  • Nitrophenols / pharmacology*
  • Norepinephrine / pharmacology
  • Prefrontal Cortex / drug effects
  • Propylamines / pharmacology*
  • Rats
  • Rats, Long-Evans
  • Reaction Time / drug effects*
  • Reaction Time / physiology
  • Tolcapone


  • Adrenergic Uptake Inhibitors
  • Benzophenones
  • Catechol O-Methyltransferase Inhibitors
  • Central Nervous System Stimulants
  • Dopamine Uptake Inhibitors
  • Nitrophenols
  • Propylamines
  • Methylphenidate
  • Atomoxetine Hydrochloride
  • Tolcapone
  • Dextroamphetamine
  • Dopamine
  • Norepinephrine