Toward isolating the role of dopamine in the acquisition of incentive salience attribution

Abstract

Stimulus-reward learning has been heavily linked to the reward-prediction error learning hypothesis and dopaminergic function. However, some evidence suggests dopaminergic function may not strictly underlie reward-prediction error learning, but may be specific to incentive salience attribution. Utilizing a Pavlovian conditioned approach procedure consisting of two stimuli that were equally reward-predictive (both undergoing reward-prediction error learning) but functionally distinct in regard to incentive salience (levers that elicited sign-tracking and tones that elicited goal-tracking), we tested the differential role of D1 and D2 dopamine receptors and nucleus accumbens dopamine in the acquisition of sign- and goal-tracking behavior and their associated conditioned reinforcing value within individuals. Overall, the results revealed that both D1 and D2 inhibition disrupted performance of sign- and goal-tracking. However, D1 inhibition specifically prevented the acquisition of sign-tracking to a lever, instead promoting goal-tracking and decreasing its conditioned reinforcing value, while neither D1 nor D2 signaling was required for goal-tracking in response to a tone. Likewise, nucleus accumbens dopaminergic lesions disrupted acquisition of sign-tracking to a lever, while leaving goal-tracking in response to a tone unaffected. Collectively, these results are the first evidence of an intraindividual dissociation of dopaminergic function in incentive salience attribution from reward-prediction error learning, indicating that incentive salience, reward-prediction error, and their associated dopaminergic signaling exist within individuals and are stimulus-specific. Thus, individual differences in incentive salience attribution may be reflective of a differential balance in dopaminergic function that may bias toward the attribution of incentive salience, relative to reward-prediction error learning only.

Keywords: Dopamine; Goal-tracking; Incentive salience; Sign-tracking.

Figure 1

The effects of a dopamine receptor antagonist on sign- and goal-tracking during 2-CS PCA acquisition, while the drugs were onboard. Mean (± SEM) response rate (responses/second; r/s) for the effects of SCH-23390 (0.01 mg/kg) on (A) sign-tracking and (C) goal-tracking. Mean (± SEM) response rate (responses/second; r/s) for the effects of eticlopride (0.01 mg/kg) on (B) sign-tracking and (D) goal-tracking. Mean (± SEM) difference in response probability (ST probability – GT probability) for a lever CS and tone CS during 2-CS PCA training for (E) SCH-23390 (0.01 mg/kg) and (F) eticlopride (0.01 mg/kg) compared against a saline control group. 1.0 indicates exclusive sign-tracking while −1.0 indicates exclusice goal-tracking.

Figure 2

Sign- and goal-tracking responses to a lever and tone CS during a drug-free CS-only test to identify what was learned under treatment conditions during 2-CS PCA acquisition. The legend refers to the pretreatments each group received during 2-CS PCA acquisition. Mean (± SEM) response rate (responses/second; r/s) for individuals pretreated with SCH-23390 (0.01 mg/kg), eticlopride (0.01 mg/kg), and saline during acquisition on (A) sign-tracking and (B) goal-tracking. Note: data not present (i.e., no bar in the graph) for goal-tracking in response to a lever CS in saline pretreated animals directly reflects no goal-tracking behavior measured for that group.

Figure 3

The conditioned reinforcing value attributed to the lever or tone CS during drug-free tests post 2-CS PCA training. The legend refers to the pretreatments each group received during 2-CS PCA acquisition. Mean (± SEM) number of active nosepokes that produced the previously learned stimulus for SCH-23390 (0.01 mg/kg), eticlopride (0.01 mg/kg), and saline pretreated groups during 2-CS PCA acquisition and mean (± SEM) number of inactive nosepokes that results in no consequences for SCH-23390 (0.01 mg/kg), eticlopride (0.01 mg/kg), and saline pretreated groups during 2-CS PCA acquisition.

Figure 4

The acute effects of (A) SCH-23390 and (B) eticlopride on CS preference, post 2-CS PCA training, where the relative value of the lever CS is directly compared to that of the tone CS. Mean (± SEM) % choice for the lever CS as a function of increasing odds against [(1 – p)/p] food delivery following the lever CS. Lines are choice functions defined by s/(1 + k(odds against)), (s) sensitivity to lever CS value; (k) discounting rate of lever CS value.

Figure 5

The effects of 6-OHDA lesion on 2-CS PCA acquisition. Mean (± SEM) response rate (responses/second; r/s) for the (A) sign-tracking and (B) goal-tracking. Mean (± SEM) difference in response probability (ST probability – GT probability) for a lever CS and tone CS during 2-CS PCA training (C). 1.0 indicates exclusive sign-tracking while −1.0 indicates exclusive goal-tracking.