Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine.
Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine.
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DOI：
10.1186/1756-6606-4-12
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发表时间：
2011-03-16
期刊：
影响因子：
3.6
通讯作者：
Suzuki H
中科院分区：
文献类型：
--
作者：
Kobayashi K;Ikeda Y;Suzuki H
选择性5-羟色胺再吸收抑制剂（SSRI）被广泛用于治疗情绪和焦虑症。然而，SSRIs的有益和不利影响的神经元基础仍然知之甚少。我们最近发现，SSRI氟西汀可以逆转成年小鼠海马颗粒细胞的成熟状态。颗粒细胞的“去成熟”是在大量颗粒细胞中诱导的，并且极大地改变了这些细胞的功能和生理特性。在这里，我们表明，这种独特形式的神经元可塑性与小鼠行为的明显变化相关。我们用氟西汀长期治疗成年雄性小鼠，并检查其对小鼠几种行为形式的影响。在氟西汀治疗期间，小鼠显示出笼内活动水平的日间波动显著增加，其特征在于在几天内偶尔在活动减退和活动过度之间转换。这种不稳定的笼活动伴随着焦虑相关行为的增加，并且可以在氟西汀停药后长达4周观察到。如前所述，氟西汀引起的颗粒细胞去成熟包括颗粒细胞输出、苔藓纤维、突触的突触易化降低至幼年水平。苔藓纤维突触促进检查电生理急性海马切片也仍然抑制氟西汀停药后，并显着相关的波动笼活动水平在个别小鼠。此外，在缺乏5-HT 4受体的小鼠中，颗粒细胞的退化已被证明是减弱的，氟西汀对笼活动水平的波动没有显著影响。我们的研究结果表明，SSRI氟西汀可以诱导小鼠在熟悉的环境中的活动水平的显着的日常变化，并且海马颗粒细胞的去成熟与这种不稳定行为的表达密切相关。基于这些结果，我们提出，颗粒细胞的不成熟可能是一个潜在的细胞基础的开关样变化的行为状态与SSRI治疗。
Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat mood and anxiety disorders. However, neuronal bases for both beneficial and adverse effects of SSRIs remain poorly understood. We have recently shown that the SSRI fluoxetine can reverse the state of maturation of hippocampal granule cells in adult mice. The granule cell "dematuration" is induced in a large population of granule cells, and greatly changes functional and physiological properties of these cells. Here we show that this unique form of neuronal plasticity is correlated with a distinct change in behavior of mice. We chronically treated adult male mice with fluoxetine, and examined its effect on several forms of behavior of mice. During fluoxetine treatments, mice showed a marked increase in day-to-day fluctuations of home cage activity levels that was characterized by occasional switching between hypoactivity and hyperactivity within a few days. This destabilized cage activity was accompanied by increased anxiety-related behaviors and could be observed up to 4 weeks after withdrawal from fluoxetine. As reported previously, the granule cell dematuration by fluoxetine includes a reduction of synaptic facilitation at the granule cell output, mossy fiber, synapse to the juvenile level. Mossy fiber synaptic facilitation examined electrophysiologically in acute hippocampal slices also remained suppressed after fluoxetine withdrawal and significantly correlated with the fluctuation of cage activity levels in individual mice. Furthermore, in mice lacking the 5-HT4 receptor, in which the granule cell dematuration has been shown to be attenuated, fluoxetine had no significant effect on the fluctuation of cage activity levels. Our results demonstrate that the SSRI fluoxetine can induce marked day-to-day changes in activity levels of mice in the familiar environment, and that the dematuration of the hippocampal granule cells is closely associated with the expression of this destabilized behavior. Based on these results, we propose that the granule cell dematuration can be a potential cellular basis underlying switching-like changes in the behavioral state associated with SSRI treatments.
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影响因子：
56.9
作者：
Santarelli, L;Saxe, M;Hen, R
通讯作者：
Hen, R
DOI：
10.1038/npp.2009.47
发表时间：
2009-09
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.5
作者：
Marchal, C;Mulle, C
通讯作者：
Mulle, C
DOI：
10.1177/070674370304800410
发表时间：
2003-05-01
影响因子：
4
作者：
Ali, S;Milev, R
通讯作者：
Milev, R
影响因子：
2.7
作者：
Cassel, JC;Cassel, S;Jarrard, L
通讯作者：
Jarrard, L