FACILITATION OF DOPAMINE RELEASE INVIVO BY SEROTONIN AGONISTS - STUDIES WITH MICRODIALYSIS
FACILITATION OF DOPAMINE RELEASE INVIVO BY SEROTONIN AGONISTS - STUDIES WITH MICRODIALYSIS
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DOI：
10.1016/0014-2999(91)90658-d
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发表时间：
1991-07-23
影响因子：
5
通讯作者：
GALLOWAY, MP
中科院分区：
文献类型：
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作者：
BENLOUCIF, S;GALLOWAY, MP
在麻醉大鼠前纹状体灌注5-羟色胺受体激动剂的同时，通过微透析监测神经元外多巴胺（DA）水平的变化，以及DA和5-羟色胺（5-HT）的代谢物。灌注5-HT以剂量依赖性的方式促进DA释放，并且在更大程度上比任何其他激动剂测试。灌注0.04 nmol 5-HT时神经元外DA水平升高34%，灌注4.0 nmol 5-HT时神经元外DA水平升高18倍。灌注多剂量的1-（m-氯苯基）哌嗪（m-CPP）或三氟甲基苯基哌嗪（TFMPP）也导致DA释放的剂量依赖性促进，0.4 nmol m-CPP或10.0 nmol TFMPP产生的细胞外DA增加40%。40.0 nmol m-CPP使DA增加50倍，160 nmol TFMPP使DA增加11倍。局部应用5-甲氧基-3（1,2,3,6-四氢-4-吡啶基）- 1h吲哚琥珀酸酯（RU24969）或8-羟基-2-（二-正丙胺）四溴化萘（8-OH-DPAT） （2.0 nmol灌注超过20分钟）分别使细胞外DA增加300和40%。8-OH-DPAT （100 μ g/kg）预处理后，RU24969 （2.0 nmol）也促进DA的释放。灌注芬氟拉明释放内源性5-羟色胺也以剂量依赖的方式增加神经元外DA，而用5-羟色胺再摄取抑制剂氟西汀预处理可以阻止这种促进作用。用5-HT1拮抗剂品多洛尔（4.0 nmol）预处理可降低0.4 nmol 5-HT对DA释放的促进作用。这些结果表明，前纹状体的5 -羟色胺能神经支配可能对DA的释放有促进作用。
Using microdialysis, changes in extraneuronal levels of dopamine (DA), and the metabolites of DA and serotonin (5-HT), were monitored concurrent with perfusion of 5-HT1 agonists into the anterior striata of anesthetized rats. Perfusion of 5-HT facilitated DA release in a dose dependent manner, and to a greater extent than any other agonist tested. Extraneuronal DA levels increased 34% with perfusion of 0.04 nmol 5-HT and 18-fold with perfusion of 4.0 nmol 5-HT. Perfusion with multiple doses of either 1-(m-chlorophenyl)piperazine (m-CPP) or trifluoromethylphenylpiperazine (TFMPP) also resulted in a dose-dependent facilitation of DA release with a 40% increase in extracellular DA produced by either 0.4 nmol m-CPP or 10.0 nmol TFMPP. A 50-fold increase in DA followed 40.0 nmol m-CPP, while 160 nmol TFMPP enhanced DA 11-fold. Local application of either 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole succinate (RU24969) or 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) (2.0 nmol perfused over 20 min) increased extracellular DA by 300 and 40%, respectively. RU24969 (2.0 nmol) also facilitated DA release following systemic pretreatment with 8-OH-DPAT (100-mu-g/kg). Perfusion with fenfluramine to release endogenous 5-HT also increased extraneuronal DA in a dose-dependent manner, and this facilitation was prevented by pretreatment with the 5-HT reuptake inhibitor fluoxetine. The facilitation of DA release by 0.4 nmol 5-HT was reduced by pretreatment with the 5-HT1 antagonist pindolol (4.0 nmol). These results suggest that serotonergic innervation of the anterior striatum may exert a facilatory influence on DA release.