Department of Psychological and Brain Sciences, Krieger School of Arts and Sciences, Johns Hopkins University, 3400 N Charles St, 224 Dunning Hall, Baltimore, MD, 21218, USA.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Eur J Neurosci. 2017 Aug;46(4):2047-2055. doi: 10.1111/ejn.13642. Epub 2017 Aug 1.
The attribution of incentive salience to reward-paired cues is dependent on dopamine release in the nucleus accumbens core (NAcC). These dopamine signals conform to traditional reward-prediction error signals and have been shown to diminish with time. Here we examined whether the diminishing dopamine signal in the NAcC has functional implications for the expression of sign-tracking, a Pavlovian conditioned response indicative of the attribution of incentive salience to reward-paired cues. Food-restricted male Sprague Dawley rats were trained in a Pavlovian paradigm in which an insertable lever predicted delivery of food reward in a nearby food cup. After 7 or 14 training sessions, rats received infusions of saline, the dopamine antagonist flupenthixol, or the GABA agonists baclofen and muscimol into the NAcC or the dorsal lateral striatum (DLS). Dopamine antagonism within the NAcC attenuated sign-tracking, whereas reversible inactivation did not affect sign-tracking but increased non-specific food cup checking behaviors. Neither drug in the DLS affected sign-tracking behavior. Critically, extended training did not alter these effects. Although extended experience with an incentive stimulus may reduce cue-evoked dopamine in the NAcC, this does not remove the dependence on dopamine in this region to promote Pavlovian cue approach nor result in the recruitment of dorsal lateral striatal systems for this behavior. These data support the notion that dopamine within the mesoaccumbal system, but not the nigrostriatal system, contributes critically to incentive motivational processes independent of the length of training.
奖励线索的激励显著性归因于伏隔核核心(NAcC)中的多巴胺释放。这些多巴胺信号符合传统的奖励预测误差信号,并随着时间的推移而减少。在这里,我们研究了 NAcC 中多巴胺信号的减少是否对标志追踪的表达具有功能意义,标志追踪是一种表明对奖励线索赋予激励显著性的条件反应。在一个 Pavlovian 范式中,对禁食的雄性 Sprague Dawley 大鼠进行了训练,其中可插入的杠杆预测在附近的食物杯中提供食物奖励。经过 7 或 14 次训练课程后,大鼠接受了 NAcC 或背外侧纹状体(DLS)中盐水、多巴胺拮抗剂氟哌噻吨和 GABA 激动剂巴氯芬和 muscimol 的输注。NAcC 内的多巴胺拮抗作用减弱了标志追踪,而可逆失活则不会影响标志追踪,但会增加非特异性食物杯检查行为。DLS 中的任何一种药物都不会影响标志追踪行为。关键是,延长训练不会改变这些影响。尽管对激励刺激的长期经验可能会减少 NAcC 中的线索诱发多巴胺,但这并不会消除该区域对促进 Pavlovian 线索接近的多巴胺依赖性,也不会导致背外侧纹状体系统招募该行为。这些数据支持这样一种观点,即中脑伏隔核系统中的多巴胺,而不是黑质纹状体系统中的多巴胺,对独立于训练长度的激励动机过程具有至关重要的贡献。