Initially-neutral cues paired with rewards are thought to acquire motivational significance, as if the incentive motivational value of the reward is transferred to the cue. Such cues may serve as secondary reinforcers to establish new learning, modulate the performance of instrumental action (Pavlovian-instrumental transfer, PIT), and be the targets of approach and other cue-directed behaviors. Here we examined the effects of lesions of the ventral striatal nucleus accumbens (ACb) and the basolateral amygdala (BLA) on the acquisition of discriminative autoshaped lever-pressing in rats. Insertion of one lever into the experimental chamber was reinforced by sucrose delivery, but insertion of another lever was not reinforced. Although sucrose was delivered independently of the rats’ behavior, sham-lesioned rats rapidly came to press the reinforced but not the nonreinforced lever. Bilateral ACb lesions impaired the initial acquisition of sign-tracking but not its terminal levels. In contrast, BLA lesions produced substantial deficits in terminal levels of sign-tracking. Furthermore, whereas ACb lesions primarily affected the probability of lever press responses, BLA lesions mostly affected the rate of responding once it occurred. Finally, disconnection lesions that disrupted communication between ACb and BLA produced both sets of deficits. We suggest that ACb is important for initial acquisition of consummatory-like responses that incorporate hedonic aspects of the reward, while BLA serves to enhance such incentive salience once it is acquired.

Cues associated with rewarding events acquire value themselves as a result of the incentive value of the reward being transferred to the cue. Consequently, presentation of a reward-paired cue can trigger reward-seeking behaviors towards the cue itself (i.e., sign-tracking). The ventral pallidum (VP) has been demonstrated to be involved in a number of motivated behaviors, both conditioned and unconditioned. However, its contribution to the acquisition of incentive value is unknown. Using a discriminative autoshaping procedure with levers, we investigated the effects of disrupting VP activity in rats on the emergence of sign-tracking using chemogenetics (Designer Receptors Exclusively Activated by Designer Drugs; DREADDs). Transient disruption of VP neurons (activation of the inhibitory hM4D(Gi) DREADD through systemic injections of clozapine N-oxide (CNO) prior to each autoshaping session) impaired acquisition of sign-tracking (lever press rate) without having any effect on approach to the site of reward delivery (i.e., goal-tracking) nor on the expression of sign-tracking after it was acquired. In addition, we conducted electrophysiological recordings in freely behaving rats following VP DREADD activation. The majority of VP units that were responsive to CNO injections exhibited rapid inhibition relative to baseline, a subset of CNO-responsive units showed delayed excitation, and a smaller subset displayed a mixed response of inhibition and excitation following CNO injections. We argue that disruption of VP during autoshaping specifically disrupted the transfer of incentive value that was attributed to the lever cue, suggesting a surprisingly fundamental role for the VP in acquiring compared to expressing Pavlovian incentive values.

Neutral cues paired with rewards often appear to acquire motivational significance, as if the incentive motivational value of the reward is transferred to the cue. Such cues have been reported to modulate the performance of instrumental action (Pavlovian-instrumental transfer, PIT), serve as conditioned reinforcers in the establishment of new learning, and be the targets of approach and other cue-directed behaviors. Here we examined the effects of lesions of the amygdala central nucleus (CeA) on the acquisition of discriminative autoshaped lever-pressing. Insertion of one lever into the experimental chamber was reinforced by sucrose delivery, but insertion of another lever was not reinforced. Although sucrose delivery was not contingent on lever pressing, both CeA- and sham-lesioned rats rapidly came to press the reinforced but not the nonreinforced lever. Despite their showing little evidence of impairments in autoshaped lever pressing, these same CeA-lesioned rats showed significant deficits in the expression of PIT in a subsequent phase of the experiment. The lack of impaired autoshaping in CeA-lesioned rats contrasts with effects previously reported for conditioned orienting responses (ORs) and for other putative measures of incentive learning including PIT and conditioned approach to visual cues.

Certain Pavlovian conditioned stimuli (CSs) paired with food unconditioned stimuli (USs) come to elicit approach and even consumption-like behaviors in rats (sign-tracking). We investigated the effects of lesions of the nucleus accumbens core (ACbC) or shell (ACbS) on the acquisition of sign-tracking in a discriminative autoshaping procedure in which presentation of one lever CS was followed by delivery of sucrose, and another was not. Although we previously found that bilateral lesions of the whole ACb disrupted the initial acquisition of sign-tracking, neither ACbC or ACbS lesions affected the rate or percentage of trials in which rats pressed the CS+. In addition, detailed video analysis showed no effect of either lesion on the topography of the sign-tracking conditioned response (CR). These and other results from lesion studies of autoshaping contrast with those from previous sign-tracking experiments that used purely visual cues (Parkinson, Robbins, and Everitt, 2000a; Parkinson, Willoughby, Robbins, and Everitt, 2000b), suggesting that the neural circuitry involved in assigning incentive value depends upon the nature of the CS.

Appetitive sign-tracking, in which reward-paired cues elicit approach that can result in cue interaction, demonstrates how cues acquire motivational value. For example, rats will approach and subsequently interact with a lever insertion cue that signals food delivery upon its retraction. However, lever deflections are rapidly reduced once rats are trained on an omission schedule in which lever interactions cancel food delivery. Here we evaluated the change in sign-tracking response topography in rats exposed to such an omission procedure. Lever deflections dropped precipitously when they canceled reward. However, rats that were on an omission schedule continued to approach, sniff, and contact the lever without pressing it, and did so at comparable rates to rats that were not under an omission schedule. Thus, sign-tracking was maintained, albeit in a different manner, following omission. Such findings show that the motivational attraction to reward cues can be expressed with remarkable persistence and flexibility.[Supplemental material is available for this article.]Appetitive sign-tracking is a phenomenon in which a rewardpaired cue elicits approach that can result in cue interaction (Brown and Jenkins 1968;Jenkins and Moore 1973;Hearst and Jenkins 1974;Boakes 1977). For example, rats will acquire a conditioned response (CR) in which they will approach, contact, and bite a lever conditioned stimulus (CS) that signals the delivery of a food unconditioned stimulus (US). Sign-tracking is a key model for studying behavioral and neural mechanisms of normal and excessive motivational attraction to reward-paired stimuli (Lajoie and Bindra 1976;Berridge 2004;Tomie et al. 2008;Flagel et al. 2010;Robinson and Berridge 2013;Huys et al. 2014;Robinson et al. 2014).Negative automaintenance, in which a lever press cancels reward, has been used to show that sign-tracking can be markedly sensitive to instrumental contingency changes (Williams and Williams 1969;Stiers and Silberberg 1974;Locurto et al. 1976), suggesting a sensitivity to response-reward associations (Skinner 1992). For example, Locurto et al. (1976) have found that lever contacts after sign-tracking are markedly reduced in rats moved to an omission schedule, with similar rates of lever contacts compared with rats exposed to extinction or random cue/reward delivery. However, typically, sign-tracking does not decline to zero (Atnip 1977;Eldridge and Pear 1987;Schwartz and Williams 1972a;Stiers and Silberberg 1974;Woodard et al. 1974), suggesting some motivational persistence as well. Thus, sign-tracking CRs may be partly sensitive to contingency and partly under control of motivational forces that promote its persistence.Generally, it remains unclear to what quantitative extent the motivational attraction to the CS actually declines along with the declining CR when it cancels reward. Is the incentive value of the CS retained but masked by reduced lever pressing measures, or is it reduced as well?To clarify this issue, we studied the response topography of sign-trac...