496 Fig. 3 Effects of morphine (a), naloxone (b), and their combi- nation (c) on the mean percent- age preference for the large reinforcer and change in prefer- ence from the 0-s delay (d) in the delayed reward paradigm. In total, n=16 animals were included in the analyses. SED standard error of differences between means. *p<0.05 versus vehicle/vehicle and +p <0.05 versus vehicle/6.0-mg/kg morphine injections Psychopharmacology (2009) 205:489–502 doses, thereby supporting the lack of a dose × delay interaction effect [F(4,60) = 1.40, ε = 0.25, p = 0.26]. The number of omissions to start a trial (range, 1.03 ± 0.23 to 1.67 ± 0.35 omissions/block) was not significantly affected by morphine [dose: F(4,60) = 1.71, p = 0.16; dose × delay: F (16,240) = 1.22, p = 0.25]. It should be noted that in two individuals, 6.0 mg/kg morphine did bias choice towards one response option irrespective of the delay. One animal preferably chose the response alternative associated with the immediate small reward, whereas the other mainly preferred the delayed large reward. All other rats displayed a delay-dependent decrease in preference for the large reward at this dose of morphine, although the majority did show a modest reduction in choice for the large reward at the 0-s delay with 6.0 mg/kg morphine. Excluding these two individuals with biased choice from the analyses did not alter the main findings with morphine [dose: F(4,52) = 2.72, p = 0.039; dose × delay: F(16,208) = 1.05, p = 0.40]. Naloxone slightly but significantly shifted the preference for the larger delayed reward (Fig. 3b) [dose: F(3,45) = 0.46, p = 0.71; dose × delay: F(12,180) = 2.04, ε = 0.66, p = 0.048]. However, further comparisons revealed no significant dose × delay interaction effects of naloxone at any dose compared with vehicle. This suggests that the overall dose × delay interaction effect lacks biological significance. Further analyses of the steepness of the discounting curves supported this notion [F(3,45) = 1.19, ε = 0.44, p = 0.31]. Similarly, naloxone did not affect the number of omissions to start a trial [dose: F(3,45) = 2.28, ε = 0.65, p = 0.12; dose × delay: F(12,180) = 1.07, p = 0.39]. In the combination study (Fig. 3c), the effects of 6.0 mg/kg morphine were antagonized by naloxone [dose: F(3,45) = 4.63, ε = 0.74, p = 0.014; dose × delay: F(12,180) = 2.62, ε = 0.93, p = 0.004], and further comparisons showed that this was the case for 1.0 mg/kg naloxone. This significant dose × delay interaction effect was further sub- stantiated by the slope analysis of the discounting curves [F (3,45) = 2.91, ε = 0.51, p = 0.045] which revealed significant differences in steepness of the slopes between vehicle– vehicle versus vehicle–morphine and 0.3 mg/kg naloxone– morphine. Similar to the morphine dose–response experiment, one individual always preferred the response alternative associated with the immediate small reward. Excluding this individual from the analyses did not change the main findings [dose: F(3,42) = 3.77, ε = 0.71, p = 0.032; dose × delay: F(12,168) = 2.46, ε = 0.89, p = 0.008].