Chronic fluvoxamine treatment changes 5-HT_<2A/2C>receptor-mediated behavior in olfactory bulbectomized mice
Chronic fluvoxamine treatment changes 5-HT_<2A/2C>receptor-mediated behavior in olfactory bulbectomized mice
复制标题
慢性氟伏沙明治疗改变嗅球切除小鼠的 5-HT_<2A/2C> 受体介导的行为
DOI：
10.1016/j.lfs.2012.11.005
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发表时间：
2012
期刊：
影响因子：
6.1
通讯作者：
Tadano T
中科院分区：
文献类型：
--
作者：
Oba A;Nakagawasai O;Onogi H;NemotoW;Yaoita F;Arai Y;Tan-No K;Tadano T
啮齿类动物AIMSOlfactory bulbectomy （OBX）是一种有价值的抑郁症实验模型。本研究旨在进一步阐明OBX小鼠血清素能神经元变性的影响，并评估一种广泛使用的抗抑郁药对OBX诱导的血清素能相关行为改变的影响。主要方法成年雄性小鼠采用双侧OBX或假手术治疗。5-羟色胺（5-HT）2A/ 2c受体激动剂2,5-二甲氧基-4-碘安非他明（DOI）增强OBX小鼠的头抽搐反应（HTR）。观察5-HT2A、5- ht2拮抗剂和氟伏沙明在给药后对OBX小鼠的影响。主要发现：术后第14天，与对照组相比，给药DOI （0.5mg/kg和1mg/kg， ig）引起的HTR增加约2倍。注射5- ht2a受体拮抗剂酮色林（0.025mg/kg, i.p）可抑制doi诱导的OBX后HTR的增强。同样，5- ht2c受体拮抗剂SB 242084 （1mg/kg, s.c）也能抑制doi诱导的OBX小鼠HTR。抗抑郁药氟伏沙明是一种选择性5 -羟色胺再摄取抑制剂（SSRI），慢性而非急性治疗可抑制OBX术后doi诱导的HTR增强。这些发现表明OBX以及随后从嗅球突出的神经元的变性导致5-HT2A/ 2c受体的超敏感，这可能与抑郁症症状有关。
AIMSOlfactory bulbectomy (OBX) in rodents represents a valuable experimental model of depression. This study was designed to shed further light on the impact of putative serotonergic neuronal degeneration in OBX mice and to assess the effect of a widely used antidepressant on serotonergic related behavioral changes induced by OBX.MAIN METHODSAdult male ddY mice were subject to bilateral OBX or sham surgery. The serotonin (5-HT)2A/2Creceptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) enhanced a head-twitch response (HTR) in OBX mice. Effects of 5-HT2A, 5-HT2Cantagonists and fluvoxamine were observed in OBX mice following DOI administration.KEY FINDINGSThe HTR elicited by the administration of DOI (0.5mg/kg and 1mg/kg, i.p.) was increased about twofold in OBX mice when compared with controls on the 14th day after the surgery. The injection of ketanserin (0.025mg/kg, i.p.), a 5-HT2Areceptor antagonist, inhibited the enhancement of the DOI-induced HTR after OBX. Likewise, the administration of SB 242084 (1mg/kg, s.c.), a 5-HT2Creceptor antagonist, also inhibited the DOI-induced HTR in OBX mice. Chronic but not acute treatment with the antidepressant fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), suppressed the enhancement of DOI-induced HTR after OBX.SIGNIFICANCEThese findings indicate that OBX, and the subsequent degeneration of neurons projecting from the olfactory bulb, caused a supersensitivity of 5-HT2A/2Creceptors which may be involved in symptoms of depression.