title: Examining the role of dopamine D2 and D3 receptors in Pavlovian conditioned approach behaviors.
abstract: 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 (0.01-0.32mg/kg) or pramipexole (0.032-0.32mg/kg), the D2/D3 antagonist raclopride (0.1mg/kg), and the selective D3 antagonist, SB-277011A (6 or 24mg/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.
authors.affiliation: Undergraduate Program in Neuroscience, University of Michigan, Ann Arbor, MI, United States; Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Kurt M
authors.initials: KM
authors.lastname: Fraser
authors.affiliation: Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Haight
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, United States.
authors.forename: Eliot L
authors.initials: EL
authors.lastname: Gardner
authors.affiliation: Undergraduate Program in Neuroscience, University of Michigan, Ann Arbor, MI, United States; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, United States; Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States. Electronic address: sflagel@umich.edu.
authors.forename: Shelly B
authors.initials: SB
authors.lastname: Flagel
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D003463:Cues; D015259:Dopamine Agents / Q000494:pharmacology; D006040:Goals; D008297:Male; D009042:Motivation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012054:Reinforcement, Psychology
chemical_list: D015259:Dopamine Agents; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3
keywords: D(2) receptor; D(3) receptor; Dopamine; Goal-tracking; Motivation; Sign-tracking