Cornish J L, Kalivas P W
Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
J Neurosci. 2000 Aug 1;20(15):RC89. doi: 10.1523/JNEUROSCI.20-15-j0006.2000.
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.
伏隔核中多巴胺传递的增强被认为是可卡因成瘾的主要介导因素。然而，反复接触可卡因与谷氨酸传递的增加有关。这就提出了一种可能性，即可卡因成瘾所特有的行为，如渴望引发的复吸，可能并非优先由多巴胺传递介导。一种复吸动物模型被用于证明，谷氨酸而非伏隔核中的多巴胺传递，是可卡因诱导的觅药行为恢复的主要介导因素。通过全身注射可卡因或向伏隔核微量注射谷氨酸受体激动剂AMPA或多巴胺来产生行为恢复。研究发现，向伏隔核微量注射AMPA受体拮抗剂可阻断所有化合物引发的行为恢复，而多巴胺受体拮抗剂仅能有效阻断通过向伏隔核内注射多巴胺所引发的行为恢复。这些数据表明，伏隔核谷氨酸而非多巴胺传递在可卡因诱导的觅药行为复吸中起重要作用。
