Psychopharmacology (2009) 205:489–502 DOI 10.1007/s00213-009-1558-8 ORIGINAL INVESTIGATION Acute effects of morphine on distinct forms of impulsive behavior in rats Tommy Pattij & Dustin Schetters & Mieke C. W. Janssen & Joost Wiskerke & Anton N. M. Schoffelmeer Received: 24 October 2008 / Accepted: 27 April 2009 / Published online: 13 May 2009 # The Author(s) 2009. This article is published with open access at Springerlink.com Abstract Rationale Disturbances in impulse control are key features of substance abuse disorders, and conversely, many drugs of abuse are known to elicit impulsive behavior both clinically and preclinically. To date, little is known with respect to the involvement of the opioid system in impulsive behavior, although recent findings have demon- strated its involvement in delay discounting processes. The aim of the present study was to further investigate the role of the opioid system in varieties of impulsivity. Materials and methods To this end, groups of rats were trained in the five-choice serial reaction time task (5- CSRTT) and stop-signal task (SST), operant paradigms that provide measures of inhibitory control and response inhibition, respectively. In addition, another group of rats was trained in the delayed reward paradigm, which measures the sensitivity towards delay of gratification and as such assesses impulsive choice. Results and discussion Results demonstrated that mor- phine, a selective µ-opioid receptor agonist, primarily impaired inhibitory control in the 5-CSRTT by increasing premature responding. In addition, in keeping with previous data, morphine decreased the preference for the large over small reward in the delayed reward paradigm. The effects of morphine on measures of impulsivity in both the 5- CSRTT and delayed reward paradigm were blocked by naloxone, a µ-opioid receptor antagonist. Naloxone by T. Pattij (*) : D. Schetters : M. C. W. Janssen : J. Wiskerke : A. N. M. Schoffelmeer Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, Center for Neurogenomics and Cognitive Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands e-mail: t.pattij@vumc.nl itself did not alter impulsive behavior, suggesting limited involvement of an endogenous opioid tone in impulsivity. Response inhibition measured in the SST was neither altered by morphine nor naloxone, although some baseline-dependent effects of morphine on response inhibi- tion were observed. Conclusion In conclusion, the present data demonstrate that acute challenges with morphine modulate distinct forms of impulsive behavior, thereby suggesting a role for the opioid system in impulsivity. Keywords Cognition . Inhibitory control . Impulsive choice . Morphine . Naloxone Introduction A commonly observed effect of many substances of abuse and in particular psychostimulants such as amphetamine, cocaine, and nicotine is that they impair behavioral inhibition and increase impulsivity in humans (Fillmore et al. 2002; Mitchell 2004) as well as laboratory animals (Cole and Robbins 1987, 1989; Harrison et al. 1997; Paine and Olmstead 2004; Van Gaalen et al. 2006a). Furthermore, a wealth of findings have demonstrated that chronic psychos- timulant abuse is associated with a variety of cognitive disturbances including elevated levels of impulsivity (e.g., Clark et al. 2006; Coffey et al. 2003; Ersche et al. 2008; Kirby and Petry 2004; Monterosso et al. 2005; Verdejo- Garcia et al. 2007; for review, see Perry and Carroll 2008). However, somewhat contradictory findings have been reported in laboratory animals depending on forced (Jentsch et al. 2002; Paine et al. 2003; Simon et al. 2007) or volitional administration of psychostimulant drugs (Dalley et al. 2005a, b, 2007; but see, Winstanley et al. 2009).