Activation of 5-HT(1B/1D) receptors in the mesolimbic dopamine system increases dopamine release from the nucleus accumbens: a microdialysis study.
Activation of 5-HT(1B/1D) receptors in the mesolimbic dopamine system increases dopamine release from the nucleus accumbens: a microdialysis study.
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中脑边缘多巴胺系统中 5-HT(1B/1D) 受体的激活会增加伏隔核中多巴胺的释放：一项微透析研究。
DOI：
10.1016/s0014-2999(01)00913-x
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发表时间：
2001
影响因子：
5
通讯作者：
Yan,SE
中科院分区：
文献类型：
--
作者：
Yan,QS;Yan,SE
本研究旨在探讨位于中脑腹侧被盖区和延髓背核的5-羟色胺（5-HT）1B受体在多巴胺能神经元传递调节中的作用。通过逆行微透析将选择性5-HT_（1B）受体激动剂CP 93129 {3-（1，2，5，6-tetrahydro-4-pyridyl）pyrrolo[3，2-B] pyridone-5-one}注入自由活动的Sprague-Dawley大鼠腹侧被盖区或延髓核。分别用单探针和双探针微透析法测定了中脑内和被盖内CP 93129对中脑核细胞外多巴胺水平的影响。对于双探针微透析，一个探针在腹侧被盖区用于给药，另一个探针在同侧延髓核用于多巴胺测量。结果表明，向延髓核内输注CP 93129（2、5和10 μM）可以浓度相关方式增加局部多巴胺水平。向腹侧被盖区输注CP 93129（10和20 μM）也增加了同侧延髓核中的多巴胺水平。5-HT 1B/1A受体拮抗剂cyanopindolol（5 μM）可拮抗CP 93129引起的丘脑核或被盖核多巴胺释放的增加，而高选择性5-HT 1A受体拮抗剂WAY-100635（5 μM）则不能拮抗CP 93129引起的多巴胺释放。此外，脑内注射CP 93129引起的中脑核多巴胺释放增加对河豚毒素Na+通道阻断敏感。这些结果并不反对腹侧被盖区和延髓核内的5-HT_（1B）受体都参与调节中脑边缘多巴胺系统终末区多巴胺释放的观点。
This study was designed to investigate the role of 5-hydroxytryptamine (5-HT)1Breceptors located in the ventral tegmental area and nucleus accumbens in the modulation of accumbal dopaminergic transmission. The selective 5-HT1Breceptor agonist CP 93129 {3-(1,2,5,6-tetrahydro-4-pyridyl)pyrrolo[3,2-b]pyrid-5-one} was administered into the ventral tegmental area or nucleus accumbens of freely moving Sprague–Dawley rats via retrograde microdialysis. The effects of intra-accumbal and intra-tegmental CP 93129 on extracellular dopamine levels in the nucleus accumbens were measured using one- and dual-probe microdialysis, respectively. For dual-probe microdialysis, one probe was in the ventral tegmental area for drug administration and the other in the ipsilateral nucleus accumbens for dopamine measurement. The results show that infusion of CP 93129 (2, 5 and 10 μM) into the nucleus accumbens increased local dopamine levels in a concentration-related manner. Infusion of CP 93129 (10 and 20 μM) into the ventral tegmental area also increased dopamine levels in the ipsilateral nucleus accumbens. The increased dopamine release in the nucleus accumbens produced by intra-accumbal or intra-tegmental CP 93129 was antagonized by co-infusion of cyanopindolol (5 μM), a 5-HT1B/1Areceptor antagonist, but not by WAY-100635 {N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridinyl-cyclohexanecarboxamide} (5 μM), a highly selective 5-HT1Areceptor antagonist. In addition, augmentations of dopamine release in the nucleus accumbens induced by intra-accumbal CP 93129 were sensitive to Na+channel blockade with tetrodotoxin. These results are not in opposition to the concept that 5-HT1Breceptors within the ventral tegmental area and nucleus accumbens are all involved in the modulation of dopamine release in the terminal area of the mesolimbic dopamine system.