Psychopharmacology (2012) 220:771–785 0.125 mg/infusion did not differ from 0.5 mg/infusion of cocaine. Taking responses were not altered by changing the reward magnitude (F3, 33=1.951, NS; Fig. 1b). Figure 1c shows that α-flupenthixol decreased cocaine seeking in a dose-dependent manner (F3, 27= 23.829, p<0.001). Post- hoc analyses showed that 0.25 and 0.5 mg/kg α- flupenthixol differ from each other and from all other treatments. α-Flupenthixol treatment also reduced taking responses (F3, 27 = 93.429, p < 0.001; Fig. 1d): 0.25 and 0.5 mg/kg α-flupenthixol differed significantly from all other treatments. As shown in Table 1, there was no effect of α-flupenthixol on responding for cocaine during the following (drug-free) self-administration session (seeking, F3, 27 = 0.968, NS; taking, F3, 27 = 0.355, NS). Furthermore, 0.5 mg/kg α-flupenthixol suppressed seeking to a greater extent than that seeking was suppressed in the first reward omission session (t23 = 6.824, p < 0.001). There was a small but significant difference in taking between the 0 mg/kg α-flupenthixol group and the last baseline session preced- ing the first reward omission session (t23 = 3.432, p < 0.05), indicating a small difference in baseline taking levels between these groups. Nevertheless, both 0.25 and 0.5 mg/kg α-flupenthixol suppressed taking to a greater extent than during the first reward omission session (0.25 mg/kg α- flupenthixol vs. first extinction session t23=3.895, p=0.001; 0.5 mg/kg α-flupenthixol vs. first extinction session t23= 16.469, p<0.001). Both seeking and taking were affected when animals were exposed to reward omission (Fig. 1e, f). Seeking already decreased during the first reward omission session compared to the last baseline session (t14=5.152, p<0.001), and in the subsequent reward omission sessions, seeking gradually declined further (F9, 126= 12.408, p<0.001; Fig. 1e). When cocaine was reintroduced, seeking increased compared to the last reward omission session (t14=−8.094, p<0.001) but responding did not return to pre-reward omission levels until the second reacquisition session (baseline vs. first reacquisi- tion session, t14 = 3.820, p < 0.005; baseline vs. second reacquisition session, t14= 1.767, NS; baseline vs. third reacquisition session, t14=1.556, NS; baseline vs. fourth 777 reacquisition session, t14 = 1.948, NS; baseline vs. fifth reacquisition session, t14=2.365, p=0.033). Compared to the last baseline session, taking did not change during the first reward omission session (baseline vs. first reward omission session, t14=1.871, p<0.082), but in the subsequent reward omission sessions, taking gradually did decrease (F9, 126= 6.765, p<0.001; Fig. 1f). When cocaine was reintroduced, the taking response increased compared to the last reward omission session (t14=3.969, p=0.001), and responding on the taking lever did return to pre-reward omission levels (baseline vs. first reacquisition session, t14= 1.293, NS; baseline vs. second reacquisition session, t14=1.468, NS; baseline vs. third reacquisition session, t14= 1.000, NS; baseline vs. fourth reacquisition session, t14=1.871, NS; baseline vs. fifth reacquisition session, t14=1.740, NS). ST(PR) schedule with cocaine reinforcement For the ST(PR) experiments with cocaine, animals reached stable levels of responding with an average of 16.3 ± 0.5 rewards/session (range 13.0–19.6 rewards/session). The average baseline session time was 274.4 ± 8.8 min. Thus, sessions took approximately 2.5 h longer than the ST(RI) schedule session with cocaine reinforcement. Figure 2a shows that varying the magnitude of the cocaine reward resulted in a dose-dependent increase in breakpoints under an ST(PR) schedule of reinforcement (χ(2)2 = 12.286, p < 0.01). Post hoc analyses showed that all unit doses of cocaine tested differed from each other (0.125 vs. 0.25 mg/ infusion, Z6 = −2.366, p < 0.05; 0.25 vs. 0.5 mg/infusion, Z6 = −2.197, p<0.05; 0.125 vs. 0.5 mg/infusion, Z6=−2.366, p < 0.05). α-Flupenthixol decreased the breakpoints for cocaine in a dose-dependent manner (χ(3)2=22.898, p< 0.001; Fig. 2b). Post hoc analysis showed that 0.25 and 0.5 mg/kg α-flupenthixol significantly differed from saline pretreatment and from each other (0 vs. 0.25 mg/kg, Z9 = −2.397, p < 0.05; 0 vs. 0.5 mg/kg, Z9 = −2.805, p < 0.01; 0.25 vs. 0.5 mg/kg, Z9 = −2.090, p < 0.05). There was no effect of α-flupenthixol on responding during the next, drug-free self-administration session (χ(3)2 = 2.224, NS; Table 1 The results on seeking and taking in the self-administration sessions following sessions in which animals were treated with α-flupenthixol α-Flupenthixol ST(RI)cocaine ST(PR)cocaine ST(RI)sucrose ST(PR)sucrose (mg/kg, i.p.) 0 0.05 0.25 0.50 Seeking (presses/min) Taking (number) Seeking (breakpoint) Seeking (presses/min) Taking (number) Seeking (breakpoint) 10.5±2.1 9.7±0.2 142.9±31.4 24.0±4.5 8.9±0.7 119.6±23.4 9.2 ±1.6 9.5±0.2 176.8±33.5 24.0±5.8 8.8±1.5 104.3±13.5 8.0 ±1.3 9.6±0.2 166.7±26.3 23.3±4.4 8.7±0.5 138.7±12.6 8.8 ±1.5 9.5±0.3 163.9±19.2 16.7±3.1 8.1±1.3 107.3±21.7 Data are presented as mean number of lever presses ± SEM. There were no significant effects of α-flupenthixol on responding in the following self-administration sessions