title: Dissociable effects of monoamine reuptake inhibitors on distinct forms of impulsive behavior in rats.
abstract: BACKGROUND
  High levels of impulsivity are a core symptom of psychiatric disorders such as ADHD, mania, personality disorders and drug addiction. The effectiveness of drugs targeting dopamine (DA), noradrenaline (NA) and/or serotonin (5-HT) in the treatment of impulse control disorders emphasizes the role of monoaminergic neurotransmission in impulsivity. However, impulsive behavior is behaviorally and neurally heterogeneous, and several caveats remain in our understanding of the role of monoamines in impulse control.
  
  
  OBJECTIVE
  This study aims to investigate the role of DA, NA and 5-HT in two main behavioral dimensions of impulsivity.
  
  
  METHODS
  The effects of selective DA (GBR12909; 2.5-10 mg/kg), NA (atomoxetine; 0.3-3.0 mg/kg) and 5-HT (citalopram; 0.3-3.0 mg/kg) reuptake inhibitors as well as amphetamine (0.25-1.0 mg/kg) were evaluated on impulsive action in the five-choice serial reaction time task (5-CSRTT) and impulsive choice in the delayed reward task (DRT). In the 5-CSRTT, neuropharmacological challenges were performed under baseline and long intertrial interval (ITI) conditions to enhance impulsive behavior in the task.
  
  
  RESULTS
  Amphetamine and GBR12909 increased impulsive action and perseverative responding and decreased accuracy and response latency in the 5-CSRTT. Atomoxetine increased errors of omission and response latency under baseline conditions in the 5-CSRTT. Under a long ITI, atomoxetine also reduced premature and perseverative responding and increased accuracy. Citalopram improved impulse control in the 5-CSRTT. Amphetamine and GBR12909, but not citalopram or atomoxetine, reduced impulsive choice in the DRT.
  
  
  CONCLUSIONS
  Elevation of DA neurotransmission increases impulsive action and reduces impulsive choice. Increasing NA or 5-HT neurotransmission reduces impulsive action.
authors: Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, UMC Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
authors: Petra J J
authors: PJ
authors: Baarendse
authors: Louk J M J
authors: LJ
authors: Vanderschuren
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000661:Amphetamine / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D021461:Animals, Outbred Strains; D000069445:Atomoxetine Hydrochloride; D002755:Choice Behavior / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology / Q000627:therapeutic use; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007175:Impulsive Behavior / Q000188:drug therapy*; D008297:Male; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011437:Propylamines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D012691:Serial Learning / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000661:Amphetamine; D000069445:Atomoxetine Hydrochloride; D015283:Citalopram; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D011437:Propylamines; D017367:Selective Serotonin Reuptake Inhibitors; C461261:(1-(2-(bis(4-fluorophenyl)methoxy)ethyl)-4-(3-hydroxy-3-phenylpropyl) piperazinyl decanoate)