Involvement of the dorsal striatum in cue-controlled cocaine seeking
Involvement of the dorsal striatum in cue-controlled cocaine seeking
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DOI：
10.1523/jneurosci.0925-05.2005
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发表时间：
2005-09-21
影响因子：
5.3
通讯作者：
Everitt, BJ
中科院分区：
文献类型：
--
作者：
Vanderschuren, LJMJ;Di Ciano, P;Everitt, BJ
通过与药物滥用的内感受效应的关联，中性环境刺激本身可以获得动机特性，成为条件强化物，可以唤起药物寻求的渴望和复发。伏隔核多巴胺（DA）神经传递在可卡因本身的强化作用中起重要作用，但与伏隔核谷氨酸不同，它似乎不介导可卡因配对刺激的条件强化特性。相反，在可卡因寻求过程中，背纹状体的多巴胺传递在二级强化过程中得到增强，这取决于可卡因相关刺激的条件强化特性。因此，本研究的目的是评估DA和谷氨酸在背纹状体中的传递在线索控制的可卡因寻求中的作用。向背纹状体输注DA受体拮抗剂α -氟苯乙醇可在二级强化过程中减少可卡因寻求。此外，纹状体内注入AMPA/kainate （KA）受体拮抗剂LY293558 （3SR, 4aRS, 6RS, 8aRS-6-[2-(iH-tetrazol-5-yl)乙基]-1,2,3,4,4a,5,6,7,8,8 - a-十氢异喹啉- 3-羧酸），而不是NMDA受体拮抗剂AP-5，也减少了线索控制的可卡因寻求。这些数据表明，刺激背纹状体中的DA和AMPA/KA受体对于依赖于可卡因相关刺激的强化效应的药物寻找至关重要。此外，鉴于背纹状体在刺激反应习惯学习中的重要性，这些数据表明，持续寻求药物的习惯性或强迫性取决于背纹状体机制。
Through association with the interoceptive effects of drugs of abuse, neutral environmental stimuli can gain motivational properties themselves, becoming conditioned reinforcers that can evoke craving and relapse to drug seeking. Nucleus accumbens dopamine (DA) neurotransmission plays an important role in the reinforcing effect of cocaine itself, but, unlike nucleus accumbens glutamate, it seems not to mediate the conditioned reinforcing properties of cocaine-paired stimuli. Dorsal striatal DA transmission, in contrast, has been shown to be enhanced during cocaine seeking under a second- order schedule of reinforcement, which depends on the conditioned reinforcing properties of cocaine-associated stimuli. Therefore, the aim of the present study was to evaluate the role of DA and glutamate transmission in the dorsal striatum in cue-controlled cocaine seeking. Infusion of the DA receptor antagonist alpha-flupenthixol into the dorsal striatum decreased cocaine seeking under a second- order schedule of reinforcement. In addition, intradorsal striatal infusion of the AMPA/kainate (KA) receptor antagonist LY293558 (3SR, 4aRS, 6RS, 8aRS-6-[2-(iH-tetrazol-5-yl) ethyl]-1,2,3,4,4a,5,6,7,8,8a-decahydroiso-quinoline- 3-carboxylic acid), but not the NMDA receptor antagonist AP-5, also decreased cue-controlled cocaine seeking. These data show that stimulation of DA and AMPA/KA receptors in the dorsal striatum is critical for well established drug seeking that depends on the reinforcing effects of cocaine-associated stimuli. In addition, given the importance of the dorsal striatum in stimulus response habit learning, these data suggest that the habitual or compulsive quality of persistent drug seeking depends on dorsal striatal mechanisms.