Glutamate transmission in the nucleus accumbens mediates relapse in cocaine addiction
Glutamate transmission in the nucleus accumbens mediates relapse in cocaine addiction
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DOI：
10.1523/jneurosci.20-15-j0006.2000
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发表时间：
2000-08-01
影响因子：
5.3
通讯作者：
Kalivas, PW
中科院分区：
文献类型：
--
作者：
Cornish, JL;Kalivas, PW
伏隔核中多巴胺传递的升高被认为是可卡因成瘾的主要媒介。然而，反复暴露于可卡因与谷氨酸传递的招募有关。这提出了一种可能性，即可卡因成瘾的行为特征，如渴望诱导的复发，可能不是由多巴胺传递优先介导的。一个动物复发模型被用来证明谷氨酸，而不是多巴胺在伏隔核的传递，是可卡因诱导的药物寻求行为恢复的主要介质。通过全身注射可卡因或在伏隔核中微量注射谷氨酸受体激动剂AMPA或多巴胺来恢复。研究发现，在伏隔核中微量注射AMPA受体拮抗剂可阻断所有化合物的恢复，而多巴胺受体拮抗剂仅能有效阻断伏隔核内多巴胺的恢复。这些数据表明伏隔核谷氨酸在可卡因诱导的药物寻求行为复发中起重要作用，而不是多巴胺传递。
Elevated dopamine transmission in the nucleus accumbens is thought to be a primary mediator of addiction to cocaine. However, repeated exposure to cocaine is associated with the recruitment of glutamate transmission. This poses the possibility that the behaviors characterizing cocaine addiction, such as craving-induced relapse, may not be preferentially mediated by dopamine transmission. An animal model of relapse was used to demonstrate that glutamate, and not dopamine transmission in the nucleus accumbens, is a primary mediator of cocaine-induced reinstatement of drug-seeking behavior. Reinstatement was produced by a systemic injection of cocaine or by the microinjection of the glutamate receptor agonist AMPA or dopamine into the nucleus accumbens. It was found that microinjection of an AMPA receptor antagonist into the nucleus accumbens blocked reinstatement by all compounds, whereas a dopamine receptor antagonist was effective only in blocking reinstatement by intra-accumbens dopamine administration. These data suggest an important role for nucleus accumbens glutamate and not dopamine transmission in cocaine-induced relapse to drug-seeking behavior.