314 al. 2008; Perry et al. 2005; Poulos et al. 1995). It is now widely recognized that impulsivity consists of various, mostly independent behavioral dimensions that can be neuroanatomi- cally and neuropharmacologically dissociated (Dalley et al. 2011; Eagle and Baunez 2010; Evenden 1999; Pattij and Vanderschuren 2008; Winstanley 2011). In general, two main subtypes of impulsive behavior are distinguished, i.e., impulsive choice and impulsive action. Impulsive choice refers to the inability to delay gratification, which is behaviorally apparent as a preference for a small, immediate gain over a larger reward that one has to wait for. Impulsive action comprises behavior resulting from a deficit in the ability to withhold responding or stop ongoing behavior. Both behavioral subtypes of impulsivity appear in the patient population and these can be studied in preclinical models with high translational value (Evenden 1999; Moeller et al. 2001; Solanto et al. 2001; Winstanley 2011). Different classes of drugs are used in the treatment of disorders characterized by disrupted impulse regulation such as ADHD, personality disorders and problem gambling. The psychostimulant drugs amphetamine (Adderall™) and meth- ylphenidate (Ritalin™, Concerta™) are the first-choice treatment for ADHD, whereas the selective noradrenaline reuptake inhibitor atomoxetine (Strattera®) is a widely used alternative (Biederman and Faraone 2005). The therapeutic use of these drugs has sparked great interest in the role of monoaminergic neurotransmission in impulsivity. The pri- mary mode of action of amphetamine is to enhance monoaminergic neurotransmission by blocking the reuptake and evoking the release of dopamine (DA), noradrenaline (NA) and, to a lesser extent, serotonin (5-hydroxytryptamine, 5-HT) (Kuczenski and Segal 1989; Kuczenski et al. 1995; Ritz and Kuhar 1989; Rothman et al. 2001; Seiden et al. 1993; Sulzer et al. 1995). Administration of amphetamine has been shown to decrease impulsive choice in delay- discounting paradigms (Barbelivien et al. 2008; Cardinal et al. 2000; De Wit et al. 2002; Isles et al. 2003; Richards et al. 1999; Sun et al. 2011; Van Gaalen et al. 2006b; Wade et al. 2000; Winstanley et al. 2003, but see Evenden and Ryan 1996) but to increase premature responding, an index of impulsive action, in the five-choice serial reaction time task (5-CSRTT; Cole and Robbins 1987; 1989; Harrison et al. 1997; Murphy et al. 2008; Paterson et al. 2011; Pattij et al. 2007; Sun et al. 2011; Van Gaalen et al. 2006a). Pharmaco- logical analysis of the effects of amphetamine has indicated that DA neurotransmission plays an important, opposing role in the modulation of impulsive action and impulsive choice (Cole and Robbins 1989; Pattij et al. 2007; van Gaalen et al. 2006a, 2006b, 2009). Atomoxetine is a potent reuptake inhibitor with no appreciable affinity for the DA or 5-HT transporter (Bolden-Watson and Richelson 1993), which has been shown to be effective in the treatment of ADHD (Kratochvil et al. 2006; Simpson and Perry 2003; Spencer et Psychopharmacology (2012) 219:313–326 al. 2002; Wilens et al. 2006). Although selective inhibition of reuptake has been reported to have beneficial effects on impulsive action in the 5-CSRTT (Blondeau and Dellu- Hagedorn 2007; Navarra et al. 2008; Paine et al. 2007; Paterson et al. 2011; Robinson et al. 2008; Sun et al. 2011; Van Gaalen et al. 2006a), its effects on impulsive choice are inconclusive (Robinson et al. 2008; Sun et al. 2011; Van Gaalen et al. 2006b). Interestingly, 5-HT was the first neurotransmitter system to be implicated in impulsivity (Linnoila et al. 1983; Soubrié 1986). Selective 5-HT reuptake inhibitors (SSRIs) are not regularly prescribed as therapeutic drugs for ADHD (Biederman and Faraone 2005; Elia et al. 1999; Fone and Nutt 2005; Kutcher et al. 2004), although they are used for the treatment of other disorders associated with poor impulse control such as problem gambling, sexual addiction, personality disorders and impul- sive aggression (Coccaro and Kavoussi 1997; Hollander and Rosen 2000). Remarkably, the effects of SSRIs on different forms of impulsive behavior have not been characterized in depth (Bari et al. 2009; Evenden and Ryan 1996). Although the role of monoamine neurotransmission in impulsive behavior has been widely investigated, several caveats remain. First, as mentioned above, the consequen- ces of selective blockade of the 5-HT transporter for impulsive behavior are largely unknown. Second, beneficial effects of selective reuptake inhibitors on impulsive action (as assessed in the 5-CSRTT and stop signal task) have been consistently reported by different studies, but its effects on impulsive choice are inconclusive. Third, in studies on impulsive action using the 5-CSRTT, well- trained animals are used, which often display very low levels of impulsivity. This makes it easy to detect impair- ments in impulse control but leaves relatively little room to observe reductions in premature responding, which is most relevant from a therapeutic point of view. The present study sought to further characterize the role of monoamine neurotransmission in impulsive behavior, taking these caveats into account. To that aim, we investigated the effects of selective inhibitors of the reuptake of DA (GBR12909), (atomoxetine) and 5-HT (citalopram) on two main behavioral dimensions of impulsivity in rats. Impulsive action was studied using the 5-CSRTT (Carli et al. 1983; Robbins 2002), and the delayed reward task (DRT; Evenden and Ryan 1996) was used to measure impulsive choice. Amphetamine was also included as its effects on impulsive behavior have been well described (Eagle and Baunez 2010; Pattij and Vanderschuren 2008). To increase the possibility to observe drug-induced reduc- tions in impulsive action, we performed neuropharmaco- logical challenges in the 5-CSRTT under both baseline as well as long intertrial interval (ITI) conditions. The use of a long ITI, in which the animal unexpectedly has to wait longer for the instruction signal to appear, enhances levels