Psychopharmacology (2012) 219:313–326 DOI 10.1007/s00213-011-2576-x ORIGINAL INVESTIGATION Dissociable effects of monoamine reuptake inhibitors on distinct forms of impulsive behavior in rats Petra J. J. Baarendse & Louk J. M. J. Vanderschuren Received: 10 June 2011 / Accepted: 4 November 2011 / Published online: 3 December 2011 # The Author(s) 2011. This article is published with open access at Springerlink.com Abstract Rationale 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 neuro- transmission in impulsivity. However, impulsive behavior is behaviorally and neurally heterogeneous, and several caveats remain in our understanding of the role of mono- amines in impulse control. Objectives This study aims to investigate the role of DA, and 5-HT in two main behavioral dimensions of impulsivity. Methods The effects of selective DA (GBR12909; 2.5– 10 mg/kg), (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. P. J. J. Baarendse : L. J. M. J. Vanderschuren Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, UMC Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands L. J. M. J. Vanderschuren (*) Department of Animals in Science and Society, Division of Behavioural Neuroscience, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands e-mail: l.j.m.j.vanderschuren@umcutrecht.nl Results Amphetamine and GBR12909 increased impulsive action and perseverative responding and decreased accura- cy 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 or 5-HT neurotransmission reduces impulsive action. Keywords Impulsivity . Delayed reward . Five-choice serial reaction time task . Dopamine . Serotonin . Noradrenaline Introduction Exaggerated impulsive behavior very often has undesirable consequences. As such, impulsivity is prominent in the symptomatology of a variety of psychiatric disorders such as attention deficit/hyperactivity disorder (ADHD), drug addic- tion, problem gambling, mania and personality disorders (American Psychiatric Association 2000; Chamberlain and Sahakian 2007; Moeller et al. 2001). Moreover, impulsivity may be a behavioral marker for enhanced vulnerability to drug addiction. Poor response inhibition or enhanced impul- sive decision making predisposes adolescents for smoking, alcoholism and substance abuse (Audrain-McGovern et al. 2009; Nigg et al. 2006). Consistently, animal studies have shown that high impulsivity predicts the vulnerability to alcohol consumption, cocaine self-administration and nicotine-seeking behavior (Dalley et al. 2007; Diergaarde et