780 Fig. 4 Effect of altering reward size, α-flupenthixol, and reward omission on responding for sucrose under an ST(PR) schedule in rats. a Breakpoints for different amounts of sucrose pellets (n=10). b Effect of α-flupenthixol on breakpoints for sucrose (n =10). c Effects of reward omission and reacquisition on breakpoints; baseline response (session 0; closed symbol) followed by 20 reward omission sessions (sessions 1–20; open symbols), after which reacquisition took place (sessions 21–25; closed symbols) (n =10). Data are presented in mean breakpoints ± SEM. *p <0.05 for difference between groups (a, b) or sessions (c) (Wilcoxon signed ranks test) Fig. 5 Effect of α-flupenthixol on responding for cocaine (a) and sucrose (b) under an FR-1 schedule of reinforcement. Data are presented in mean number of lever presses ± SEM. *p<0.05 for difference compared to vehicle treatment (paired t test) Psychopharmacology (2012) 220:771–785 0.5 mg/kg, t7 = 2.376, p < 0.05). α-Flupenthixol did not affect inactive lever presses (F4, 28 = 0.605, NS). Discussion In the present study, we evaluated two variants of heterogeneous ST chain schedules of cocaine and sucrose self-administration. The main advantage of these schedules is that they explicitly separate the actions of seeking and taking a reward, thereby modeling the fact that different sets of actions are required to procure and consume drugs and natural rewards. We altered the value of the reinforcer by varying the reward size or by omitting the reward. As expected, cocaine seeking increased with increasing reward size under both schedules. The seeking data obtained under the ST(RI) schedule are consistent with Olmstead et al. (2000), and the seeking data obtained under the ST(PR) are in agreement with cocaine dose–response studies using traditional PR schedules (Hodos 1961; Winger and Woods 1985; French et al. 1995; Ward et al. 1996, 2005; Brebner et al. 2000). Under the ST(PR) schedule, increasing the unit dose of cocaine from 0.125 to 0.25 to 0.5 mg/infusion resulted in an orderly increase in breakpoints. Seeking rates under the ST (RI) schedule did differ between the cocaine unit doses of 0.125 and 0.25 mg/infusion, but there was no difference between 0.125 and 0.5 mg/infusion, or between 0.25 and 0.5 mg/infusion of cocaine. This difference between the schedules is perhaps caused by the fact that reinforcement rate is proportional to seeking rate under the ST(PR) but not under the ST(RI) schedule. Taking responses under the ST (RI) schedule were not affected by varying the reward size of cocaine. This was most likely a consequence of a ceiling effect, since animals in our experiment almost always took the maximum number of rewards under all reward size conditions. Under comparable experimental conditions regarding time-out duration and unit doses of cocaine, Olmstead et al. (2000) did observe a decrease in the number of rewards taken for the lowest unit dose of cocaine used. However, in their experiments, animals could earn more rewards in a session, and the number of rewards earned always exceeded 10 infusions, which was the maximum of infusions that could be earned in our setup. In the reward omission sessions, the absolute value of the reinforcer was reduced to zero. Omission of the cocaine reward decreased cocaine seeking under both ST schedules already in the first session. This indicates that cocaine seeking was goal-directed (cf. Olmstead et al. 2001) and had not become stimulus-driven (Dickinson 1985). Inter- estingly, a recent study has shown that after an extent of cocaine self-administration experience comparable to our