Fraser Kurt M, Haight Joshua L, Gardner Eliot L, Flagel Shelly B
Undergraduate Program in Neuroscience, University of Michigan, Ann Arbor, MI, United States; Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, United States.
Behav Brain Res. 2016 May 15;305:87-99. doi: 10.1016/j.bbr.2016.02.022. Epub 2016 Feb 22.
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.
阐明奖励线索获得充当激励刺激能力的个体差异背后的神经生物学机制，可能有助于开发出成功治疗成瘾及相关疾病的方法。我们使用信号追踪/目标追踪动物模型来研究多巴胺D2和D3受体在将激励显著性赋予奖励线索的倾向中所起的作用。在经典条件训练中，一个离散的杠杆线索与食物奖励配对，根据由此产生的条件反应，将大鼠分为信号追踪者或目标追踪者。我们研究了D2/D3激动剂7-羟基二丙基氨基四氢吡咯（0.01-0.32毫克/千克）或普拉克索（0.032-0.32毫克/千克）、D2/D3拮抗剂雷氯必利（0.1毫克/千克）以及选择性D3拮抗剂SB-277011A（6或24毫克/千克）对信号追踪和目标追踪条件反应表达的影响。杠杆线索获得了预测价值，并引发了信号追踪者和目标追踪者的条件反应，但只有信号追踪者的杠杆线索也获得了激励价值。给予7-羟基二丙基氨基四氢吡咯、普拉克索或雷氯必利后，信号追踪者和目标追踪者先前获得的条件反应表现均减弱。对于信号追踪者，D2/D3激动剂7-羟基二丙基氨基四氢吡咯也减弱了杠杆线索的条件强化特性。选择性D3拮抗剂对两种条件反应均无影响。D2/D3受体信号的改变，而非单独的D3信号改变，会暂时减弱先前获得的经典条件反应，无论该反应是否是激励动机过程的结果。这些发现表明，多巴胺D2受体的活性对于奖励线索维持其激励或预测特性至关重要。
