A chronic treatment with fluoxetine decreases 5-HT1A receptors labeling in mice selected as a genetic model of helplessness

A chronic treatment with fluoxetine decreases 5-HT1A receptors labeling in mice selected as a genetic model of helplessness
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DOI:
10.1016/s0006-8993(02)02548-9
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发表时间:
2002-05-17
期刊:
影响因子:
2.9
通讯作者:
Costentin, J
Costentin, J
中科院分区:
医学3区
文献类型:
--
作者:
Naudon, L;El Yacoubi, M;Costentin, J

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培育了两个品系的小鼠,以使其在悬尾试验中表现出相反的无助行为,即无助(HL)小鼠和非无助(NHL)小鼠。通过使用 H-3-8-OH-DPAT 对这两个系小鼠的脑切片进行放射自显影来定量 5-HT1A 受体标记。我们观察到,与 NHL 小鼠相比,HL 小鼠内侧前额叶、扣带回的 H-3-8-OH-DPAT 结合位点密度水平显着更高。运动和感觉皮质,在边缘系统的几个区域,例如海马的 CA3 区、齿状回、内侧和基底内侧杏仁核,以及背侧和中缝核。抗抑郁药氟西汀(10 mg/kg,每天腹膜内注射)持续 21 天的长期治疗显着减轻了 HL 小鼠的自发无助感,但没有改变 NHL 小鼠的行为。在长期注射氟西汀的 HL 小鼠大脑中,治疗后多个区域(其中中缝核)不再观察到 H-3-8-OH-DPAT 结合位点密度升高。相反,抗抑郁药治疗不会改变 NHL 小鼠的 H-3-8-OH-DPAT 结合位点密度。 HL 小鼠对长期氟西汀治疗的反应中 5-HT1A 受体结合密度的变化与悬尾试验中观察到的自发无助感的减弱平行,并且可能是这种行为的基础。 (C) 2002 Elsevier Science B.V. 保留所有权利。
Two lines of mice were bred for their opposite helpless behavior in the tail suspension test, i.e., helpless (HL) mice and non helpless (NHL) mice. The 5-HT1A receptor labeling was quantified by means of autoradiography with H-3-8-OH-DPAT on brain sections from mice of these two lines. We observed a significantly higher level of H-3-8-OH-DPAT binding sites density in HL mice comparatively to NHL mice, in the medial prefrontal, cingulate. motor and sensorial cortices, in several regions of the limbic system, such as CA3 field of hippocampus, dentate gyrus, medial and baso-medial amygdala, and in dorsal and median raphe nuclei. A chronic 21-day treatment with the antidepressant fluoxetine (10 mg/kg, i.p. daily) attenuated significantly the spontaneous helplessness in HL mice but did not alter the behavior of NHL mice. In the brain of HL mice chronically injected with fluoxetine, the elevated H-3-8-OH-DPAT binding sites density was no longer observed after treatment in several regions, among which the raphe nuclei. Conversely, the antidepressant treatment did not modify the H-3-8-OH-DPAT binding sites density in NHL mice. The variation of 5-HT1A receptors binding density in the HL mice in response to a chronic fluoxetine treatment parallels the attenuation of the spontaneous helplessness observed in the tail suspension test, and may underlie this behavior. (C) 2002 Elsevier Science B.V. All rights reserved.