772 motivational properties of food and drug rewards (Hodos 1961; Richardson and Roberts 1996; Arnold and Roberts 1997; Stafford et al. 1998). In PR schedules, the response requirement is systematically increased after every obtained reward. The maximum number of responses a subject performs in order to receive a single reward is referred to as the breakpoint and this breakpoint is thought to reflect the motivational value of the reward. PR schedules can be used to study addiction-like behavior since rats with prolonged cocaine or heroin self-administration experience show increased breakpoints under a PR schedule of reinforcement (Paterson and Markou 2003; Deroche-Gamonet et al. 2004; Wee et al. 2008; Lenoir and Ahmed 2008; Orio et al. 2009; but see Liu et al. 2005). Although they have enormously contributed to our understanding of the neurobehavioral processes underlying drug use and drug addiction, there is a drawback to traditional PR schedules. That is, once response criteria are met under a traditional PR schedule, the reward is delivered without requiring further action from the animal. When this reward is administered intravenously, it has no gustatory or consummatory component. Therefore, these schedules do not take into account that in real life procuring drugs takes a different set of actions than the actual consumption of drugs. In contrast, when an experimental schedule in which reward seeking and reward taking are separate actions is used, the animal has explicit control over its intake. Such a schedule also allows to study the neuro- behavioral underpinnings of reward seeking and reward taking separately. This feature is relevant because it has been shown that food seeking and food taking can be differently affected by manipulations of the motivational state of an animal (Balleine et al. 1995; Corbit and Balleine 2003). Olmstead et al. (2000) were the first to evaluate a heterogeneous seeking–taking (ST) chain schedule of reinforcement in which seeking and taking drugs were studied as two separate actions. In their setup, animals had to seek a cocaine or sucrose reward by pressing a “seeking” lever under a random interval (RI) schedule of reinforce- ment, in order to get access to a second “taking” lever, pressing which under a fixed-ratio 1 (FR-1) schedule of reinforcement resulted in delivery of the reward. They observed that, under certain conditions, the response rates on the seeking lever were proportional to the reward size for both cocaine and sucrose. Although the ST(RI) schedule has since been used to study different aspects of appetitive and addictive behavior (Olmstead et al. 2001; Johnston et al. 2001; Hellemans et al. 2002; Vanderschuren and Everitt 2004; Pelloux et al. 2007; Zapata et al. 2010), the neural and behavioral characteristics of heterogeneous ST chain schedules remain relatively unexplored. Here, we evaluated two variants of the heterogeneous ST chain schedule for sucrose and cocaine self-administration, Psychopharmacology (2012) 220:771–785 using either an RI or a PR requirement on the seeking link of the response chain. We hypothesized that changing the value of the cocaine and sucrose reward affects seeking and taking under the ST(RI) and ST(PR) schedules of rein- forcement. We manipulated the value of cocaine and sucrose in three different ways. First, we varied the magnitude of the cocaine and sucrose reward, by either changing the unit dose of cocaine, or the amount of sucrose pellets that could be earned per reinforcement. We expected that larger rewards have a higher value and would therefore evoke more seeking responses (cf. Olmstead et al. 2000). Second, we systemically administered the dopamine receptor antagonist α-flupenthixol before self-administration sessions. There is an ongoing debate about the exact role of dopaminergic neurotransmission in appetitive and hedonic processes (Wise 2004; Schultz 2007; Berridge 2007; Robbins and Everitt 2007). Suppression of dopaminergic neurotrans- mission decreases the motivation to respond for both cocaine and food, as measured under traditional PR schedules of reinforcement (Roberts et al. 1989; Hubner and Moreton 1991; Depoortere et al. 1993; Richardson et al. 1994; Cheeta et al. 1995; Smith et al. 1995; Ward et al. 1996; Aberman et al. 1998; Aberman and Salamone 1999; Reilly 1999; Caul and Brindle 2001; Bari and Pierce 2005; Zhang et al. 2005). However, this decrease in motivation could be a conse- quence of alterations in the rewarding properties of food and cocaine and/or the willingness to exert effort for a reward. It has been shown that suppression of dopamine neurotrans- mission usually attenuates responding for food under demanding effort schedules (Reilly 1999; Cheeta et al. 1995; Aberman and Salamone 1999; Caul and Brindle 2001; Salamone et al. 2001), but does not affect food intake when food is readily available or response costs are low (Salamone et al. 1991; Ikemoto and Panksepp 1996; Aberman and Salamone 1999; Baldo et al. 2002; Barbano and Cador 2006). Therefore, it is thought that dopamine decreases the willingness to respond for food, rather than its positive subjective properties. On the other hand, it has been widely shown that animals increase their cocaine intake after administration of a dopamine receptor anta- gonist when responding under low ratio schedules. It is then assumed that animals compensate for the reduced positive subjective effects by increasing their intake (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). Therefore, dopamine is thought to be important for the positive subjective properties of cocaine. However, this role for dopamine in cocaine reward value does not exclude a role for dopamine in the willingness to work for cocaine under high effort schedules as well. We hypothesized that dopamine mediates both the positive