322 rats is associated with reduced premature responding in the 5-CSRTT (Homberg et al. 2007). Conversely, forebrain 5- HT depletion significantly increases premature responding in the 5-CSRTT (Harrison et al. 1997; Winstanley et al. 2004). Together, these studies suggest that increasing 5-HT activity may be a possible mechanism for attenuation of impulsive action. In vivo microdialysis within the medial prefrontal cortex has shown a positive relationship between premature responding and basal 5-HT levels although no alteration in 5-HT efflux during task performance was found (Dalley et al. 2002). These results indicate a role for tonic 5-HT levels in the prefrontal cortex in impulsive regulation in the 5-CSRTT. However, 5-HT depletion using 5,7-DHT infusion into the medial prefrontal cortex did not affect impulsive action in the 5-CSRTT (Fletcher et al. 2009). Thus, the role of 5-HT in impulse action is not straightforward, which is likely related to the great diversity of 5-HT receptors, and the fact that 5-HT modulates impulsive action through different brain regions (Eagle and Baunez 2010; Pattij and Vanderschuren 2008). In contrast to its effects on impulsive behavior in the 5CSRTT, amphetamine had beneficial effects on impulsive choice, exemplified by the enhanced ability of the animals to choose a large, delayed reward instead of a small, immediate reward. Our finding is in keeping with previous studies in mice, rats and humans (Barbelivien et al. 2008; De Wit et al. 2002; Isles et al. 2003; Richards et al. 1999; Van Gaalen et al. 2006b; Wade et al. 2000; Winstanley et al. 2003) although this effect of amphetamine is found to be dose-, baseline- and context-dependent (Barbelivien et al. 2008; Cardinal et al. 2000; Evenden and Ryan 1996; Isles et al. 2003). In this study, we showed that impulsive choice was decreased after blockade of DA by GBR12909 but not selective blockade of or 5-HT by atomoxetine or citalopram, respectively. An important regulatory role of DA in impulsive choice has been proposed before (Wade et al. 2000; Van Gaalen et al. 2006b) as the improved impulsive choice by amphetamine was blocked by the DA D2 receptor antagonist eticlopride (Van Gaalen et al. 2006b). In the present study, atomoxetine did not affect impulsive choice. In agreement with our findings, Sun et al. (2011) found no effect on impulsive choice following atomoxetine administration. In contrast, Robinson et al. (2008) reported that atomoxetine reduced impulsive choice whereby the increase in percentage choice for the large reward after atomoxetine treatment was most pronounced at the shorter delays. The somewhat less selective reuptake blocker desipramine had no consistent effect in the DRT (Van Gaalen et al. 2006b). Together, these data suggest that acute enhancement of neurotransmission has, at best, modest effects on impulsive choice in a delayed reward task. In vivo microdialysis experiments have shown that 5-HT release within the medial prefrontal cortex correlates with Psychopharmacology (2012) 219:313–326 performance in the DRT (Winstanley et al. 2006) indicating that 5-HT release is essential for proper delay discounting judgments. However, inconsistent effects of forebrain 5-HT depletions on impulsive choice have been found (Bizot et al. 1999; Mobini et al. 2000; Winstanley et al. 2003; 2004; Wogar et al. 1993). Likewise, inconsistent effects of 5-HT depletion have been found in humans as tryptophan depletion increased delay discounting in healthy volunteers in one study (Schweighofer et al. 2008) but not another (Crean et al. 2002). In the present study, selective inhibition of 5-HT reuptake by citalopram did not affect choice behavior in the delayed reward task. In agreement with our findings, Evenden and Ryan (1996) found that the tolerance to delay of gratification was not affected by acute administration of citalopram or imipramine. Early studies on the neural mechanisms of impulsive behavior have implicated low levels of 5-HT in impulsivity (Linnoila et al. 1983; Soubrié 1986). Together with previous findings discussed here, our data indicate that elevation of 5-HT levels by SSRIs has a beneficial effect on impulsive action but not impulsive choice suggesting that the early association of 5-HT with impulsivity relates more to the former than to the latter. The present study aimed to pinpoint the separate roles of three monoamine neurotransmitters in two forms of impulsive behavior using selective DA, and 5-HT reuptake blockers. Two limitations to this approach should be mentioned. First, although GBR12909, atomoxetine and citalopram display low affinity for the other monoamine transporters (Fone and Nutt 2005; Rothman et al. 2001), transporter-selective reuptake inhibitors are not necessarily transmitter-selective reuptake inhibitors. DA reuptake in the striatum depends primarily on the DA transporter, whereas DA reuptake in the prefrontal cortex depends on both the transporter and the DA transporter due to the low density of the DA transporter in this area (Carboni et al. 2006; Morón et al. 2002; Tanda et al. 1997). Atomoxetine, therefore, indirectly boosts prefrontal cortical DA via its effects on the transporter but it does not modulate DA levels in the striatum (Bymaster et al. 2002). Thus, a contribution of prefrontal DA to the effects of atomoxetine in the 5-CSRTT cannot be excluded. However, the COMT inhibitor tolcapone that selectively modulates DA, but not NA, did not attenuate impulsive action in rats that exhibited suboptimal 5-CSRTT performance suggesting that cortical DA does not contribute to the effects of atomoxetine on impulsive action (Paterson et al. 2011). Second, through their downstream effects, increased synaptic DA, and 5-HT levels can indirectly alter the activity of other neurotransmitter systems (e.g., Di Giovanni et al. 1999; Vanderschuren et al. 1999) so that coordinated activity of multiple neurotransmitter systems mediates adaptive behav- ior. For example, with regard to impulse control, 5-HT–DA interactions have been shown to be involved in impulsive