Increased extracellular DA concentrations, such as that elicited by abused drugs, facilitate learning (Jay, 2003; Kelley, 2004), including relationships between the behavioral response to drug-related stimuli and drug-mediated reinforcement (Berke and Hyman, 2000; Nestler, 2001). For example, dorsal striatal DA release from the nigrostriatal pathway is necessary for habit learning (Faure et al., 2005), and repeated amphetamine exposure, which enhances DA levels, augments subsequent habit formation (Nelson and Killcross, 2006). Moreover, in addition to shaping learning about drug reinforcement, DA may also modulate the motivation to seek drugs independent from their perceived hedonic value (Berridge and Robinson, 1998). Intriguingly, upon repeated pairing of a natural reinforcer like sucrose and a cue that predicts that reinforcer, midbrain DA neurons no longer exhibit phasic firing for the reinforcer and only fire for the predictive cue (Schultz, 1998; Schultz, 2004). Thus, DA neuronal activation for a natural reinforcer does not occur if learned cues fulfill predicted valence expectations, which is hypothesized to facilitate adaptive responding (Schultz, 2004). In contrast, DA release following presentation of drug rewards and drug-associated cues persists (Ito et al., 2002; Kalivas and O’Brien, 2008; Volkow et al., 2006).
