5-HT1B receptor-mediated regulation of serotonin clearance in rat hippocampus in vivo
5-HT1B receptor-mediated regulation of serotonin clearance in rat hippocampus in vivo
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DOI：
10.1046/j.1471-4159.2000.0752113.x
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发表时间：
2000-11-01
影响因子：
4.7
通讯作者：
Frazer, S
中科院分区：
文献类型：
--
作者：
Daws, LC;Gould, GG;Frazer, S
5-羟色胺（5-HT; 5-羟色胺）转运体（5-HTT）在终止多巴胺能神经传递中是重要的，并且是许多精神治疗药物的主要靶点。因此，研究5-HTT活性的调节对于理解多巴胺能神经传递的控制是重要的。利用高速计时电流法，我们已经证明，局部应用5-HT 1B拮抗剂进入海马CA 3区，抑制5-HT从细胞外液（ECF）中的清除。在本研究中，我们证明，5-HT 1B拮抗剂氰基吲哚酚不产生这种效果，通过增加内源性5-HT的释放或直接结合到5-HTT。剂量反应研究表明，氰基吲哚洛尔抑制5-HT清除的效力与选择性5-HT再摄取抑制剂氟伏沙明相当。局部应用5-HT 1A拮抗剂WAY 100635并不改变5-HT清除率，表明氰基吲哚洛尔延长清除率的作用不是通过涉及5-HT 1A受体的机制。最后，低剂量的氰基吲哚洛尔和氟伏沙明抑制5-HT从ECF的清除的效果是相加的。这些数据是一致的假设，即激活终端5-HT 1B自身受体增加5-HTT的活动。
The 5-hydroxytryptamine (5-HT; serotonin) transporter (5-HTT) is important in terminating serotonergic neurotransmission and is a primary target for many psychotherapeutic drugs. Study of the regulation of 5-HTT activity is therefore important in understanding the control of serotonergic neurotransmission. Using highspeed chronoamperometry, we have demonstrated that local application of 5-HT1B antagonists into the CA3 region of the hippocampus prolongs the clearance of 5-HT from extracellular fluid (ECF). In the present study, we demonstrate that the 5-HT1B antagonist cyanopindolol does not produce this effect by increasing release of endogenous 5-HT or by directly binding to the 5-HTT. Dose-response studies showed that the potency of cyanopindolol to inhibit clearance of 5-HT was equivalent to that of the selective 5-HT reuptake inhibitor fluvoxamine. Local application of the 5-HT1A antagonist WAY 100635 did not alter 5-HT clearance, suggesting that the effect of cyanopindolol to prolong clearance is not via a mechanism involving 5-HT1A receptors. Finally, the effect of low doses of cyanopindolol and fluvoxamine to inhibit clearance of 5-HT from ECF was additive. These data are consistent with the hypothesis that activation of terminal 5-HT1B autoreceptors increases 5-HTT activity.