A PET imaging study of 5-HT1A receptors in cat brain after acute and chronic fluoxetine treatment
A PET imaging study of 5-HT1A receptors in cat brain after acute and chronic fluoxetine treatment
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DOI：
10.1016/j.neuroimage.2006.08.012
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发表时间：
2006-11-15
期刊：
影响因子：
5.7
通讯作者：
Zimmer, Luc
中科院分区：
文献类型：
--
作者：
Aznavour, Nicolas;Rbah, Latifa;Zimmer, Luc
免疫电镜和β -微探针研究表明，经选择性5-HT1A受体激动剂8-OH-DPAT或特异性5-羟色胺再摄取抑制剂氟西汀急性治疗后，血清素5-HT1A自身受体内化与大鼠中隔背核（NRD）体内[F-18]MPPF结合明显减少有关。为了确定这一事件是否与脑成像有关，本[F-18]MPPF正电子发射断层扫描（PET）研究对被麻醉的猫进行了研究，这些猫分别给予或不给予单剂量（5mg /kg，静脉注射）或长期服用氟西汀（5mg /kg，连续21天）。与对照组相比，急性氟西汀治疗后，[F-18]MPPF结合电位在猫NRD中显著（且明显）降低，而在其他脑区保持不变。出乎意料的是，慢性氟西汀治疗后，[F-18]MPPF结合电位在任何脑区均未受到影响。在大鼠的平行免疫电镜实验中，慢性氟西汀治疗后，NRD树突质膜上5-HT1A自受体的密度与对照组相当。如果在SSRI治疗开始时通过PET成像检测到[F-18]MPPF结合的减少，则可能作为疗效的生物学指标。(c) 2006爱思唯尔公司版权所有。
Immuno-electron microscopic and beta-microprobe studies have demonstrated that the internalization of serotonin 5-HT1A autoreceptors, after acute treatment with the selective 5-HT1A receptor agonist 8-OH-DPAT or with the specific serotonin reuptake inhibitor (SSRI) fluoxetine, is associated with a marked decrease in the in vivo binding of [F-18]MPPF in the nucleus raphe dorsalis (NRD) of rat. To determine whether this event might be amenable to brain imaging, the present [F-18]MPPF positron emission tomographic (PET) study was carried out in anesthetized cats given or not a single dose (5 mg/kg, i.v.) or chronically treated with fluoxetine (5 mg/kg, s.c. for 21 days). Compared to control, [F-18]MPPF binding potential was considerably (and visibly) decreased in the cat NRD after acute fluoxetine treatment, while it remained unchanged in other brain regions. Unexpectedly, after chronic fluoxetine treatment, [F-18]MPPF binding potential was not affected in any brain region. In parallel immunoelectron microscopic experiments carried out in rat, the density of 5-HT1A autoreceptors on the plasma membrane of NRD dendrites was comparable to control after chronic fluoxetine treatment. If the decrease in [F-18]MPPF binding at the onset of SSRI treatment was detectable by PET imaging, it could potentially serve as a biological index of efficacy. (c) 2006 Elsevier Inc. All rights reserved.