Differential involvement of NMDA, AMPA/kainate, and dopamine receptors in the nucleus accumbens core in the acquisition and performance of Pavlovian approach behavior

Differential involvement of NMDA, AMPA/kainate, and dopamine receptors in the nucleus accumbens core in the acquisition and performance of Pavlovian approach behavior
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DOI:
10.1523/jneurosci.21-23-09471.2001
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发表时间:
2001-12-01
影响因子:
5.3
通讯作者:
Everitt, BJ
Everitt, BJ
中科院分区:
医学1区
文献类型:
--
作者:
Di Ciano, P;Cardinal, RN;Everitt, BJ

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与初级奖赏配对的刺激可以获得情绪配价和诱发自动的巴甫洛夫接近反应的能力,这已被证明是由伏隔核介导的。本实验观察了伏隔核核中心注入谷氨酸或多巴胺受体拮抗剂对巴甫洛夫辨别方法获得食欲条件性刺激的影响。训练大鼠进行自动变形任务,在该任务中,将条件刺激(CS+;杠杆)插入操作室10秒,然后递送食物颗粒。另一个杠杆(CS-)的出现从来不是食物。受试者产生了一种有选择地接近和接触CS+的条件性反应,尽管食物递送丝毫不取决于动物的反应。观察到伏隔核内注入AP-5、LY293558[(3SR,4ARS,6RS,8aRS)-6-[2-(iH-tetrazol-5yl)ethyl]-1,2,3,4,4a,5,6,7,8,8a-decahydroiso-quinoline-3-carboxylic酸])和α-氟苯硫醇对这种条件性反应的获得和表现的影响呈三重解离。AMPA/海人藻酸受体拮抗剂LY293558阻断了辨别性接近的表现,但不影响习得,这从增加接近CS-的途径中得到了证明。相反,NMDA受体拮抗剂AP-5只损害自形的获得,而不损害自形的执行,而多巴胺D1/D2受体拮抗剂α-flupenthixol在获得和执行过程中都减少了对CS+的接近。在巴甫洛夫条件化方法的获得和表达过程中,这些受体类型与伏核核心的边缘皮质和多巴胺能传入的分离相互作用的数据被讨论。
Stimuli paired with primary rewards can acquire emotional valence and the ability to elicit automatic, Pavlovian approach responses that have been shown to be mediated by the nucleus accumbens. The present experiment investigated the effects of infusions of glutamatergic or dopaminergic receptor antagonists into the core of the nucleus accumbens on the acquisition and performance of Pavlovian discriminated approach to an appetitive conditioned stimulus. Rats were trained on an autoshaping task in which a conditioned stimulus (CS+; a lever) was inserted into the operant chamber for 10 sec, after which a food pellet was delivered. Presentation of another lever (CS-) was never followed by food. Subjects developed a conditioned response of approaching and contacting the CS+ selectively, although food delivery was not in any way contingent on the animals' response. A triple dissociation in the effects of AP-5, LY293558 [(3SR, 4aRS, 6RS, 8aRS)-6-[2-(iH-tetrazol-5yl)ethyl]-1,2,3,4,4a,5,6,7,8,8a-decahydroiso-quinoline-3-carboxylic acid], and alpha -flupenthixol infused into the nucleus accumbens core on the acquisition and performance of this conditioned response was observed. The AMPA/kainate receptor antagonist LY293558 disrupted discriminated approach performance but not acquisition, as evidenced by increased approaches to the CS-. In contrast, the NMDA receptor antagonist AP-5 impaired only the acquisition, but not performance, of autoshaping whereas the dopamine D1/D2 receptor antagonist alpha -flupenthixol decreased approaches to the CS+ during both acquisition and performance. The data are discussed with reference to dissociable interactions of these receptor types with limbic cortical and dopaminergic afferents to the nucleus accumbens core during the acquisition and expression of Pavlovian conditioned approach.