782 2007; Salamone et al. 2009), whereas for cocaine it probably mediates both (Koob et al. 1998; Wise 2004; Pierce and Kumaresan 2006). The absence of a compen- satory increase in sucrose self-administration after α- flupenthixol treatment under the FR-1 schedule of rein- forcement indicates that the dopamine receptor antagonist did not reduce the positive subjective, rewarding proper- ties of sucrose. Therefore, the effects of α-flupenthixol on sucrose seeking under the ST chain schedules were most likely the result of a reduced motivation to work for sucrose. The highest dose of α-flupenthixol tested (0.5 mg/kg, i.p.) attenuated sucrose self-administration under an FR-1 schedule of reinforcement. Since this dose of α-flupenthixol does not affect locomotor activity (Veeneman et al. 2011a), this result suggests that at a high dose, a dopamine receptor antagonist also influences the willingness to respond for sucrose under low ratio schedules. The decrease in cocaine seeking and taking under the ST chain schedules induced by α-flupenthixol can be explained by a decrease in the positive subjective, rewarding properties of cocaine. Under the FR-1 schedule, α-flupenthixol, in doses up to 0.5 mg/kg i.p., increased cocaine self-administration. This suggests that animals increased their intake to compensate for a lower reward value of cocaine, akin to the increase in responding observed under an FR-1 schedule when the unit dose of cocaine is lowered (Gerber and Wise 1989; Zittel-Lazarini et al. 2007). These findings are in agree- ment with many previous studies showing that systemic treatment with dopamine receptor antagonists increases responding for cocaine under low ratio schedules and that high doses of dopamine receptor antagonists reduce lever pressing for cocaine, likely reflecting extinction of responding (De Wit and Wise 1977; Ettenberg et al. 1982; Roberts and Vickers 1984; Koob et al. 1987; Bergman et al. 1990; Corrigall and Coen 1991; Hubner and Moreton 1991; Caine and Koob 1994). However, we hypothesized that dopamine mediates both the positive subjective, rewarding properties of cocaine and the willingness to exert effort for rewards, including cocaine. Indeed, we have several reasons to think that α- flupenthixol affected cocaine seeking under the ST schedules by reducing both the rewarding properties of cocaine and the motivation to work for the drug. First, suppressing dopamine neurotransmission affected cocaine seeking and taking to a larger extent than sucrose seeking and taking. Under the ST(RI) schedules, both cocaine seeking and taking were reduced by lower doses of α-flupenthixol, whereas only the highest dose of α-flupenthixol affected sucrose seeking. Sucrose taking was not affected at all by α- flupenthixol, whereas the dopamine receptor antagonist did reduce cocaine taking. In addition, under the ST(PR) Psychopharmacology (2012) 220:771–785 schedule, similar doses of α-flupenthixol affected breakpoints for cocaine and sucrose, but the magnitude of the effect was larger for cocaine than for sucrose. Second, comparable to sucrose, the highest dose of α-flupenthixol (0.5 mg/kg, i.p.) also reduced cocaine intake under the FR-1 schedule. Since this unit dose of cocaine (0.25 mg/infusion) is on the descending limb of the dose–response curve (Veeneman et al. 2011b), a reduction in responding under an FR-1 schedule of reinforcement is suggestive of a leftward (indicating an increase in the reward value of cocaine) or a downward shift in the dose–response curve (indicating reduced motivation for cocaine). Clearly, the latter explanation is more plausible. Third, if the role of dopamine was restricted to mediating the rewarding properties of cocaine, then the maximum effect of a dopamine receptor antagonist would be to nullify the reward value of cocaine. Hence, the largest effect of α- flupenthixol should resemble the effect of the first reward omission. However, 0.5-mg/kg α-flupenthixol attenuated cocaine seeking under the ST(RI) and the ST(PR) to a significantly larger extent than during the first reward omission session. Together, these observations support the notion that dopamine mediates cocaine reward as well as the willingness to exert effort for cocaine. We evaluated two different variants of ST chain schedules of reinforcement with either an RI or a PR requirement on the seeking link. One important differ- ence between these schedules is that under the ST(PR), but not under the ST(RI) schedule, reinforcement rate is proportional to seeking rate. Under the ST(PR) sched- ule, the number of taking opportunities directly depends on the number of seeking responses performed in a session. In our experiments, once rats got access to the taking link, they always responded on this lever and received the reward. Thus, breakpoints on the seeking lever directly reflected the number of taking responses and the number of rewards obtained. However, unlike the ST(PR) schedule, under the ST(RI) schedule, seeking rates do not automatically reflect taking rates. For example, Olmstead et al. (2000) showed that changes in cocaine reward magnitude can result in opposite effects on seeking and taking rates under an ST (RI) schedule. They showed that in the absence of a time- out period, the cocaine seeking rate increases with reward size but cocaine taking decreases with reward size. Thus, in contrast to the ST(PR) schedule, the ST(RI) schedule can be used to measure alterations in instrumental responding on the seeking and the taking links indepen- dently. Consistent with this notion, our present data show that α-flupenthixol reduced sucrose seeking but not taking under the ST(RI) schedule and that the effects of reward omission emerged faster and were of larger magnitude for seeking than for taking, for both sucrose and cocaine.