Examining the role of dopamine D₂ and D₃ receptors in Pavlovian conditioned approach behaviors

Elucidating the neurobiological mechanisms underlying individual differences in the extent to which reward cues acquire the ability to act as incentive stimuli may contribute to the development of successful treatments for addiction and related disorders. We used the sign-tracker/goal-tracker animal model to examine the role of dopamine D₂ and D₃ receptors in the propensity to attribute incentive salience to reward cues. Following Pavlovian training, wherein a discrete lever-cue was paired with food reward, rats were classified as sign- or goal-trackers based on the resultant conditioned response. We examined the effects of D₂/D₃ agonists, 7-OH-DPAT (0.01-0.32 mg/kg) or pramipexole (0.032-0.32 mg/kg), the D₂/D₃ antagonist raclopride (0.1 mg/kg), and the selective D₃ antagonist, SB-277011A (6 or 24 mg/kg), on the expression of sign- and goal-tracking conditioned responses. The lever-cue acquired predictive value and elicited a conditioned response for sign- and goal-trackers, but only for sign-trackers did it also acquire incentive value. Following administration of either 7-OH-DPAT, pramipexole, or raclopride, the performance of the previously acquired conditioned response was attenuated for both sign- and goal-trackers. For sign-trackers, the D₂/D₃ agonist, 7-OH-DPAT, also attenuated the conditioned reinforcing properties of the lever-cue. The selective D₃ antagonist did not affect either conditioned response. Alterations in D₂/D₃ receptor signaling, but not D₃ signaling alone, transiently attenuate a previously acquired Pavlovian conditioned response, regardless of whether the response is a result of incentive motivational processes. These findings suggest activity at the dopamine D₂ receptor is critical for a reward cue to maintain either its incentive or predictive qualities.