Psychopharmacology (2011) 214:769–778 773 Fig. 1 Mean (± SEM) starts latency (a), run time (b), and retreats (c) for animals running an alley for i.v. heroin or cocaine. Data were averaged across 3 days/trials. Animals ran exclusively for one drug reinforcer for 15 trials and then were switched to the alternate reinforcer for an additional 15 trials (shift denoted by the dotted vertical line) first day of runway training revealed no significant differences between the heroin- or cocaine-reinforced animals (p>0.05), suggesting that the initial disparity between the two groups seen on the first data point (averaged across trials 1–3) is attributable to performance on trials 2 and 3 (i.e., only after the rats had experienced the drugs in the goal box). Once the drug reinforcers were transposed, rats shifting from cocaine to heroin showed an immediate and reliable decrease in start latencies while animals shifting from heroin to cocaine increased their start latencies. Thus, the failure to observe any overall main effect for Trial or Group is not surprising since the reversal in group performance after the drug reinforcers were switched essentially offset the differences observed prior to the switch. Mean Group run times (± SEM) are depicted in Fig. 1b. Here, the mixed two-factor (Group × Trial) ANOVA yielded a significant main effect for Trial (F(9, 48) = 2.341, p< 0.05) and Group (F(1, 48) = 16.399, p < 0.01) as well as a Group × Trial interaction (F(9, 48) = 6.692, p < 0.01). Heroin- and cocaine-reinforced subjects initially traversed the runway at comparable speeds (trials 1–3), but over time the cocaine- reinforced rats took progressively longer to enter the goal box while heroin-reinforced animals tended to maintain or reduce their run times. When the reinforcers were trans- posed, animals moving from heroin to cocaine increased their run times (i.e., ran more slowly) while animals moving from cocaine to heroin maintained or continued to reduce their run times. Rats working for i.v. cocaine developed a conflict about goal box entry—as evidenced by a progressive increase in retreat behaviors over trials—an effect not observed in animals working for heroin (Fig. 1c, left panel). A mixed two-factor ANOVA (Group × Trial) yielded significant main effect for Trials (F(9, 48) = 27.513, p < 0.01) and a significant Group × Trial interaction (F(9, 48) = 13.810, p < 0.01), but no main effect of Group (p > 0.05). Both groups of animals exhibited few and comparable numbers of retreats during initial trials of testing, and only the cocaine-reinforced rats exhibited a progressive increase in retreat frequency as testing continued. After the two drug reinforcers were transposed, those rats transitioning from heroin to cocaine exhibited a progressive increase in retreat frequency similar to that observed in those animals that ran for cocaine during the first half of the drug self- administration session. In animals transitioning from cocaine to heroin, no additional increase in retreat frequen- cy was observed. Of course, when averaged across groups, retreat frequency tended to increase over trials (Trial effect) with the effect due primarily to the elevation in retreats observed in the heroin to cocaine subjects (Group × Trial interaction). Runway cue-induced reinstatement The responsiveness of subjects to the cocaine- or heroin- paired olfactory cues was assessed on the 7th, 14th, or 21st day of extinction. A comparison of the mean test day performance of animals that transitioned from cocaine to heroin versus those that transitioned from heroin to cocaine identified no group differences for start latencies, run times, or retreats (Bonferroni-protected independent sample t tests). Thus, the rats’ behavioral response to the cues on test day