Psychopharmacology (2007) 193:85–96 DOI 10.1007/s00213-007-0773-4 ORIGINAL INVESTIGATION Effects of the cannabinoid CB1 receptor antagonist rimonabant on distinct measures of impulsive behavior in rats Tommy Pattij & Mieke C. W. Janssen & Inga Schepers & Gustavo González-Cuevas & Taco J. de Vries & Anton N. M. Schoffelmeer Received: 6 October 2006 / Accepted: 10 March 2007 / Published online: 27 March 2007 # Springer-Verlag 2007 Abstract Rationale Pathological impulsivity is a prominent feature in several psychiatric disorders, but detailed understanding of the specific neuronal processes underlying impulsive behavior is as yet lacking. Objectives As recent findings have suggested involvement of the brain cannabinoid system in impulsivity, the present study aimed at further elucidating the role of cannabinoid CB1 receptor activation in distinct measures of impulsive behavior. Materials and methods The effects of the selective canna- binoid CB1 receptor antagonist, rimonabant (SR141716A) and agonist WIN55,212-2 were tested in various measures of impulsive behavior, namely, inhibitory control in a five- choice serial reaction time task (5-CSRTT), impulsive choice in a delayed reward paradigm, and response inhibition in a stop-signal paradigm. Results In the 5-CSRTT, SR141716A dose-dependently improved inhibitory control by decreasing the number of premature responses. Furthermore, SR141716A slightly improved attentional function, increased correct response latency, but did not affect other parameters. The CB1 receptor agonist WIN55,212-2 did not change inhibitory control in T. Pattij (*) : M. C. W. Janssen : I. Schepers : T. J. de Vries : A. N. M. Schoffelmeer Department of Anatomy and Neurosciences, Research Institute Neurosciences Vrije Universiteit, Center for Neurogenomics and Cognitive Research, VU Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands e-mail: t.pattij@vumc.nl G. González-Cuevas Laboratorio de Psicobiología, Facultad de Psicología, Campus Somosaguas, Universidad Complutense de Madrid, Madrid E-28223, Spain the 5-CSRTT and only increased response latencies and errors of omissions. Coadministration of WIN55,212-2 prevented the effects of SR141716A on inhibitory control in the 5-CSRTT. Impulsive choice and response inhibition were not affected by SR141716A at any dose, whereas WIN55,212-2 slightly impaired response inhibition but did not change impulsive choice. Conclusions The present data suggest that particularly the endocannabinoid system seems involved in some measures of impulsivity and provides further evidence for the existence of distinct forms of impulsivity that can be pharmacologically dissociated. Keywords Cannabinoid . Cognition . Inhibitory control . Impulsive choice . Response inhibition . SR141716A . WIN55,212-2 Introduction Despite its relative recent discovery, the central endocan- nabinoid system has been implicated in a variety of behaviors such as food intake (for review, see Di Marzo and Matias 2005) and nociception (for review, see Cravatt and Lichtman 2004), and in mediating the reinforcing properties of drugs of abuse (for review, see De Vries and Schoffelmeer 2005). In addition, the endocannabinoid system has been shown to play an important role in various cognitive processes. In this respect, memory encoding, retrieval, and extinction processes have received most interest (e.g., Marsicano et al. 2002; Takahashi et al. 2005; Varvel et al. 2005; for review, see Lichtman et al. 2002), presumably due to the high expression level of CB1 receptors in the hippocampal formation (Egertova and