92 Fig. 4 Effects of SR141716A on response inhibition as mea- sured in the stop-signal para- digm. Data are depicted as mean (±SEM) percentage of correctly inhibited stop trials with varying SSDs before the mean go RT (a), go reaction times (b) and estimated stop signal reaction times from SSDs 200, 100, and 50 ms (c). **p<0.005 vs vehicle Psychopharmacology (2007) 193:85–96 Discussion To our knowledge, this is the first report demonstrating behavioral effects of a CB1 receptor agonist and antagonist on independent measures of impulsivity. Thus far, evidence pointing towards cannabinoid involvement in impulsivity mainly originates from studies in which effects of THC or marijuana were tested in human volunteers (Lane et al. 2005; McDonald et al. 2003). Our data obtained in the 5- CSRTT strongly suggest that inhibitory control is modulat- ed by an endogenous cannabinoid tone, as premature responding was dose dependently decreased by SR141716A. This notion is further supported by the observation that in the presence of WIN55,212-2, the effects of 3.0 mg/kg SR141716A on premature responding were no longer observed. Furthermore, the finding that the CB1 receptor agonist WIN55,212-2, by itself, did not impair inhibitory control by increasing the number of premature responses is in keeping with previous findings (Arguello and Jentsch 2004). It should be noted though, that in the study by Arguello and Jentsch (2004), SR141716A (dose range: 0.1–1.0 mg/kg), by itself, did not change premature responding in a lateralized reaction time task, thereby, contrasting our findings. Nonetheless, differences in baseline performance may have contributed to the discrepancy in findings, as premature responding in well-trained rats in the task by Arguello and Jentsch (2004) was low (approximately 3 per session) compared to premature responding in well-trained rats in the present study (approximately 22 per session). Presumably, a floor effect may have masked the effects of SR141716A on premature responding in the lateralized reaction time task. Together, our data indicate that performance in the 5- CSRTT is associated with profound occupation of CB1 receptors by endogenously released cannabinoids. As might then be expected, the endocannabinoid uptake inhibitor AM404 did not affect inhibitory response control in the 5- CSRTT (unpublished data). In contrast to premature responding, perseverative responding after correct choice, a different measure of inhibitory control that putatively reflects compulsive behavior (Robbins 2002), was neither altered upon activation nor blockade of CB1 receptors. This