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Pavlovian stimuli previously paired with food can markedly elevate the rate of food-reinforced instrumental responding. This effect, termed Pavlovian-instrumental transfer (PIT), depends both on general activating and specific cueing properties of Pavlovian stimuli. Recent evidence suggests that the general activating properties of Pavlovian stimuli are mediated by mesoaccumbens dopamine systems; however, the role of NAC dopamine D1 and D2 receptors is still unknown. Here we examined the effects of a selective dopamine D1 and D2 receptor blockade in the shell and core subregion of the NAC on general PIT. Rats were trained to press a single lever for food, and the effect of a single Pavlovian stimulus previously associated with the same food on performance of that lever was measured in extinction. Results reveal that PIT, that is, the increase in instrumental responding during presentation of the Pavlovian stimulus, was reduced by microinjections of the dopamine D1 receptor antagonist SCH-23390 and, less pronounced, by microinjections of the dopamine D2 receptor antagonist raclopride into the NAC core or shell, respectively. Our data suggest that dopamine D1 and D2 receptors in the NAC core and shell mediate the general activating effects of Pavlovian stimuli on instrumental behavior.

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The anterior cingulate cortex (ACC) plays a critical role in stimulus-reinforcement learning and reward-guided selection of actions. Here we conducted a series of experiments to further elucidate the role of the ACC in instrumental behavior involving effort-based decision-making and instrumental learning guided by reward-predictive stimuli. In Experiment 1, rats were trained on a cost-benefit T-maze task in which they could either choose to climb a barrier to obtain a high reward (four pellets) in one arm or a low reward (two pellets) in the other with no barrier present. In line with previous studies, our data reveal that rats with quinolinic acid lesions of the ACC selected the response involving less work and smaller reward. Experiment 2 demonstrates that breaking points of instrumental performance under a progressive ratio schedule were similar in sham-lesioned and ACC-lesioned rats. Thus, lesions of the ACC did not interfere with the effort a rat is willing to expend to obtain a specific reward in this test. In a subsequent task, we examined effort-based decision-making in a lever-press task where rats had the choice between pressing a lever to receive preferred food pellets under a progressive ratio schedule, or free feeding on a less preferred food, i.e. lab chow. Results show that sham-and ACC-lesioned animals had similar breaking points and ingested comparable amounts of less-preferred food. Together, the results of Experiment 1 and 2 suggest that the ACC plays a role in evaluating how much effort to expend for reward; however, the ACC is not necessary in all situations requiring an assessment of costs and benefits. In Experiment 3 we investigated learning and reversal learning of instrumental responses guided by reward predictive stimuli. A reaction time (RT) task demanding conditioned lever release was used in which the upcoming reward magnitude (five vs. one food pellet) was signalled in advance by discriminative visual stimuli. Results revealed that rats with ACC lesions were able to discriminate reward magnitude-predictive stimuli and to adapt instrumental behavior to reversed stimulus-reward magnitude contingencies. Thus, in a simple discrimination task as used here, the ACC appears not to be required to discriminate reward magnitude-predictive stimuli and to use the learned significance of the stimuli to guide instrumental behavior.

The anterior cingulate cortex (ACC) has been implicated in encoding whether or not an action is worth performing in view of the expected benefit and the cost of performing the action. Dopamine input to the ACC may be critical for this form of effort-based decision making; however, the role of distinct ACC dopamine receptors is yet unknown. Therefore, we examined in rats the effects of an intra-ACC D1 and D2 receptor blockade on effort-based decision making tested in a T-maze cost-benefit task. In this task, subjects could either choose to climb a barrier to obtain a high reward in one arm or a low reward in the other arm without a barrier. Unlike vehicle-treated rats, rats with intra-ACC infusion of the D1 receptor antagonist SCH23390 exhibited a reduced preference for the high-costhigh-reward response option when having the choice to obtain a low reward with little effort. In contrast, in rats with intra-ACC infusion of the D2 receptor antagonist eticlopride, the preference for the high-cost-high-reward response option was not altered relative to vehicle-treated rats. These data provide the first evidence that D1 receptors in the ACC regulate effort-based decision making.In order to make adaptive decisions, subjects have to analyze costs and benefits of the available response options. A number of studies indicate that the anterior cingulate cortex (ACC), a major subregion of the prefrontal cortex, is involved in these evaluative processes and might serve to encode whether or not an action is worth performing in view of the expected benefit and the cost of performing the action (Rushworth et al. 2004). For instance, after excitotoxic ACC lesions, rats no longer selected the high-costhigh-reward option in a cost-benefit T-maze task if having the choice between climbing a barrier to obtain a large reward in one arm or to run for a low reward into the other arm with no barrier present (Walton et al. 2003).There is a large body of evidence to suggest that mesolimbic dopamine (DA) fibers projecting to the nucleus accumbens are critical for enabling an organism to overcome response costs to gain access to greater reward (Salamone et al. 1997). Recent studies indicate that mesocortical DA fibers projecting to the ACC (Berger et al. 1991) may be important in effort-based decision making as well. Like rats with excitotoxic lesions, rats with DA depletion of the ACC no longer chose effortful but high-reward action in a T-maze cost-benefit task . However, using the same task Walton et al. (2005) reported that DA depletion of the ACC had no effect on effort-based decision making. As Schweimer et al. (2005) infused a markedly higher dose of the catecholaminergic neurotoxin 6-hydroxydopamine into the ACC than Walton et al. (2005), different magnitudes of DA depletions may largely account for the discrepant results. Together, these two studies suggest that a substantial loss of DA in the ACC may be necessary to impair effort-based decision making.Prefrontal DA plays an essential role in cognitive processes and regulates aspect...