Psychopharmacology (2012) 220:771–785 This procedure was similar to the ST(RI-120) with cocaine as the reward, with the following exceptions. Training started with a “shaping” session, in which the rats received two sucrose pellets every minute for 1 h; throughout the experiment, animals were rewarded with sucrose pellets, the time-out period after receiving the reward was 1 min, and sessions lasted for a maximum of 30 min. When rats showed a stable seeking response rate for two sucrose pellets per reward (defined as less than 15% variation in presses per minute on the seeking lever over three consecutive sessions and no up- or downward trend), we performed a between-session dose–response curve for the following reward magnitudes according to a Latin square design: one sucrose pellet, two sucrose pellets, or four sucrose pellets per reward. Next, the effect of α-flupenthixol (0, 0.05, 0.25, or 0.5 mg/kg i.p., 30 min before the start of the session according to a Latin square design) was tested. This was followed by a reward omission phase. Procedures during reward omission sessions were similar as during sucrose sessions, except that animals did not receive a reward after pressing the taking lever. After 10 reward omission sessions, reacquisition of responding for sucrose (two pellets/reward) was performed. ST(PR) schedule with sucrose reinforcement Rats were trained to lever press for sucrose under a heterogeneous ST chain schedule of reinforcement with a PR requirement on the seeking link (ST(PR)). This procedure was similar to the ST(PR)cocaine procedure, with the following exceptions. Training started with a “shaping” session, in which the rats received two sucrose pellets every minute for 1 h, and the time-out period after receiving the reward was 30 s. When rats showed a stable seeking response rate for two sucrose pellets per reward (defined as no up- or downward trend and no more than four reward variations for three consecutive days), rats were allowed to press for either one or four sucrose pellets. When individual animals showed a stable response rate for this reward size, they were switched to the size they had not yet received. Next, the effect of α-flupenthixol (0, 0.05, 0.25, or 0.5 mg/kg i.p., 30 min before the start of the session according to a Latin square design) was tested. A separate group of animals was trained to respond for two sucrose pellets per reward under the ST(PR) schedule. After showing stable breakpoints, these rats underwent reward omission. After 20 reward omission sessions, responding for sucrose was reacquired. FR-1 schedule with cocaine or sucrose reinforcement Rats were trained to lever press for cocaine or sucrose under an FR-1 schedule of reinforcement. During these 2 h sessions, 775 two levers were present. In the sessions in which animals were trained to self-administer cocaine, pressing the active lever immediately resulted in the infusion of 0.25 mg cocaine in 0.1 ml saline delivered over 5.6 s, the illumination of the cue light above the active lever for 5.6 s, the retraction of both levers, and the switching off of the house light. After a 20 s time-out period, the levers were reintroduced and the house light illuminated, signaling the start of a new cycle. Pressing the inactive lever had no programmed consequences. Once animals had acquired stable self-administration under the FR-1 schedule, the effect of α-flupenthixol (0, 0.05, 0.125, 0.25, or 0.5 mg/kg i.p., 30 min before the start of the session) was tested. α-Flupenthixol injections were administered according to a Latin square design and were separated by at least two sessions without treatment. A second group of rats was trained to lever press for sucrose. This procedure was similar to the one in which the animals were responding for cocaine, except that animals were rewarded with two sucrose pellets instead of a cocaine infusion and that sessions lasted for 30 min. Drugs Cocaine-HCl (Bufa BV, Uitgeest, The Netherlands) and cis- (Z)-α-flupenthixol dihydrochloride (Sigma, Zwijndrecht, The Netherlands) were dissolved in sterile physiological saline (0.9%NaCl). Data analysis and statistics Approximately 8% of the animals trained under the ST(RI) schedules and approximately 3% of the rats trained under the ST(PR) schedules did not reach stable baseline seeking rates and were therefore excluded from the analysis. Seeking under the ST(RI) schedule was expressed as presses per minute and the seeking under the ST(PR) schedule was expressed as breakpoints. Taking responses under the ST(RI), ST(PR), and FR-1 schedules were measured using total number of responses in a session. In the experiments where reward magnitude was varied, the value used for analyses was the average of the last three sessions in which the rats showed stable responding. Experiments in which the animals were responding under an ST(RI) or FR-1 schedule in which the reward magnitude was varied or the effects of α-flupenthixol were tested were analyzed using a repeated measures ANOVA, and where appropriate, post hoc comparisons were made using a paired t test. We also tested if there was an effect of α-flupenthixol on responding in the following self-administration session via repeated measures ANOVA. Reward omission experiments under the ST(RI) schedule were analyzed by planned comparisons between the baseline and the first reward omission session, between baseline and reacquisition sessions,