86 Elphick 2000; Tsou et al. 1998). High densities of CB1 receptors are also present in frontal cortical and striatal regions (Egertova and Elphick 2000; Tsou et al. 1998), suggesting involvement of the endocannabinoid system in executive functions that appear to be largely controlled by frontal corticostriatal systems (for review, see Miller and Cohen 2001). Indeed, several clinical and preclinical observations have demonstrated that Δ9-tetrahydrocan- nabinol (THC), the principle active cannabinoid of Cannabis sativa and other synthetic cannabimimetics impair selective attention (Arguello and Jentsch 2004; Solowij et al. 1995; Verrico et al. 2004) and behavioral flexibility (Egerton et al. 2005; Hill et al. 2006), alter time estimation (Han and Robinson 2001, McDonald et al. 2003), and impair working memory (Ilan et al. 2004; Jentsch et al. 1997). Nonetheless, to date, little is known about the involvement of the endocannabinoid system in other executive functions such as inhibitory control processes subserving impulsivity. Pathological levels of impulsive behavior are important features in attention-deficit/hyperactivity disorder, sub- stance-related disorders, bipolar disorders and personality disorders (American Psychiatric Association 2000). Further elucidating the neurobiological basis of impulsivity may therefore enhance our understanding of these psychiatric disorders. It is becoming increasingly clear, however, that the concept impulsivity is multifaceted and covers various distinct and independent measures. These measures range from poor inhibitory control (impulsive action) to proba- bility and delay aversion or impulsive choice (Barkley 1997; Evenden 1999; Moeller et al. 2001). Recent studies have implicated CB1 receptors in some of these measures of impulsivity. For instance, it has been shown that acute THC impairs response inhibition in healthy volunteers, whereas time estimation and impulsive choice were not affected (McDonald et al. 2003). On the other hand, it has been demonstrated more recently that marijuana acutely increases risk taking in volunteers (Lane et al. 2005). Collectively, these data suggest a role of the cannabinoid system in impulsivity, although its precise role therein is still unclear. The present experiments were aimed at further elucidat- ing the importance of cannabinoid CB1 receptor activation on distinct measures of impulsivity. To this end, we tested the effects of the potent and selective CB1 receptor antagonist rimonabant (SR141716A; Rinaldi-Carmona et al. 1994) and agonist WIN55,212-2 (D’Ambra et al. 1992) on impulsive behavior in various operant paradigms measuring different and presumably independent aspects of impulsivity (for review, see Winstanley et al. 2006), namely, (1) the five- choice serial reaction time task to measure inhibitory control; (2) the delayed reward paradigm to measure impulsive choice, and (3) the stop-signal paradigm to measure response inhibition. Psychopharmacology (2007) 193:85–96 Materials and methods Subjects In total, 48 male Wistar rats were obtained from Harlan CPB (Horst, The Netherlands). At the start of the experi- ments, animals were 12 weeks old, weighed approximately 250 g, and were housed in pairs in macrolon cages (42.5× 26.6 × 18.5 cm; l× w× h) under a reversed 12 h light/dark cycle (lights on at 7:00 P.M.) at controlled room temperature (21 ± 2°C) and relative humidity of 60 ± 15%. Animals were maintained at approximately 90% of their free-feeding weight, starting 1 week before the beginning of the experiments by restricting the amount of standard rodent food pellets (Harlan Teklad Global Diet, Blackthorn, UK). Water was available ad libitum throughout the entire experiment. All experiments were conducted with the approval of the animal ethical committee of the Vrije Universiteit, Amsterdam, The Netherlands. Apparatus Experiments were conducted in 12 identical rat five-hole nose poke operant chambers with stainless steel grid floors (MED-NPW-5L, Med Associates, St. Albans, VT, USA) housed in sound-insulating and ventilated cubicles. Set in the curved wall of each box was an array of five circular holes, 2.54 cm in diameter, 2.2 cm deep, and 2.25 cm above floor level. Each hole was equipped with an infrared detector located across each nose poke unit 1.0 cm from the front, and a yellow LED stimulus light (6.4 mm in diameter). Rodent food pellets (45 mg, Formula P, Research Diets, New Brunswick, NJ, USA) could be delivered at the opposite wall via a dispenser. In addition, the chamber could be illuminated by a white houselight, and sound stimuli were generated using a programmable audio generator (ANL-926, Med Associates). A computer equipped with MED-PC version 1.17 (Med Associates) controlled experimental sessions and recorded data. Ani- mals were tested once daily from Monday until Friday, during the dark phase of the light/dark cycle. Behavioral procedures Separate groups of n=16 animals were trained for each different paradigm, and for all procedures, a similar habituation and magazine training protocol was used. This protocol consisted of a habituation exposure to the boxes for 20 min with the houselight on and the food cup containing three food pellets for two consecutive sessions. Subsequent- ly, in the next two sessions, in total, 100 pellets were delivered with an average delay of 15 s, to allow the animals to associate the sound of pellet delivery with reward.