Psychopharmacology (2009) 205:489–502 observations. Indeed, in a parallel study, we found that repeated exposure to 6 mg/kg morphine appeared to induce tolerance to this “disruptive” effect of the opiate at the 0-s delay, whereas at larger delays, morphine still significantly reduced preference for the larger reward. Notwithstanding these possible confounds, the fact that naloxone blocked morphine’s effects in the delayed reward indicates a µ-receptor-dependent mechanism. A possible mechanism of action by which morphine might elevate impulsive behavior is through its modulatory action on mesolimbic dopamine transmission. Opiates such as heroin and morphine enhance dopamine transmission in the nucleus accumbens (e.g., Di Chiara and Imperato 1986, 1988; Rada et al. 1991; Shoaib et al. 1995; Wise et al. 1995). These effects are primarily mediated through µ- opioid-mediated disinhibition of dopamine neuron activity in the ventral tegmental area (e.g., Kalivas et al. 1990; Spanagel et al. 1992). We have previously shown that the detrimental effects of psychostimulants on impulsivity in the 5-CSRTT largely depend on dopamine receptor activa- tion (Van Gaalen et al. 2006a). More specifically, previous studies have pinpointed the nucleus accumbens (Cole and Robbins 1989; Murphy et al. 2008) and in particular dopamine within this brain region as critical (Cole and Robbins 1987; Pattij et al. 2007b). Thus, increments in accumbal dopamine transmission might explain the effects of morphine on inhibitory control in the 5-CSRTT. Alternatively, altered dopamine function in the prefrontal cortex has been related to impulse action in the 5-CSRTT (Dalley et al. 2002). Nonetheless, doses of morphine that elevate extracellular dopamine in the nucleus accumbens were ineffective in altering dopamine in the prefrontal cortex (Bassareo et al. 1996). Furthermore, other basal ganglia and connected nuclei, such as the subthalamic nucleus (Baunez and Robbins 1997) and pedunculopontine tegmental nucleus (Inglis et al. 2001), have been implicated in impulsivity in the 5-CSRTT. To our knowledge, no studies have directly examined (1) dopaminergic modula- tion of impulsive action or (2) opioid modulation of dopamine transmission within these nuclei. Taken together, future work should elucidate whether altered dopamine transmission and which specific brain regions are critically involved in morphine-induced impulsivity. Whether opioid modulation of mesolimbic dopamine transmission is responsible for the decrease in preference for the large over small reward induced by morphine also remains a topic for further experiments. Given previous data, this seems an unlikely explanation. In contrast to the aforementioned detrimental effects of elevating dopamine transmission on impulsive action, in general, elevating dopamine transmission results in more self-controlled decisions in rodent delayed reward paradigms (Cardinal et al. 2000; Isles et al. 2003; Van Gaalen et al. 2006b; 499 Wade et al. 2000; Winstanley et al. 2005; for review, Pattij and Vanderschuren 2008) and in healthy volunteers (De Wit et al. 2002). Alternatively, acute challenges with morphine at doses of 5 mg/kg have been demonstrated to reduce extracel- lular levels of noradrenaline in the prefrontal cortex (Devoto et al. 2002; Rossetti et al. 1993), presumably mediated via presynaptic µ-opioid receptors on noradren- ergic nerve terminals in the cortex (Mulder et al. 1987). Yet, to our knowledge, no evidence is available unequivocally demonstrating a role for cortical noradrenaline in impulsive choice. However, the α2 adrenoceptor agonist clonidine induces impulsive choice in the delayed reward paradigm (Van Gaalen et al. 2006b). Presumably, this effect is mediated through activation of presynaptic α2 receptors, which in turn strongly inhibits noradrenergic neurotrans- mission (Starke 2001). Furthermore, recent findings dem- onstrate that increasing noradrenaline transmission by the selective noradrenaline reuptake inhibitor atomoxetine reduces impulsivity in the delayed reward paradigm (Robinson et al. 2008), a finding that is possibly explained by the effects of atomoxetine on cortical noradrenaline transmission (Bymaster et al. 2002; Swanson et al. 2006). Taken together, two conclusions can be drawn from the present data. First, our findings provide evidence that acute challenges with morphine impair measures of inhibitory control. Second, in support of previous data demonstrating acute morphine effects on impulsive decision making (Kieres et al. 2004), our findings also suggest acute opioid effects on this measure of impulsivity. Accumulating evidence has now implicated impulsivity in the vulnerability towards and maintenance of drug addiction (see for reviews, Perry and Carroll 2008; Verdejo-Garcia et al. 2008). In view of this, an implication of our findings might be that the acute effects of opiates on impulsivity partly contribute to the persistence of opiate use. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which per- mits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. References Band GP, van der Molen MW, Logan GD (2003) Horse-race model simulations of the stop-signal procedure. 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