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西酞普兰在应激诱导性快感缺失小鼠模型中的选择性作用及慢性应激对照研究

Selective effects of citalopram in a mouse model of stress-induced anhedonia with a control for chronic stress.

作者信息

Strekalova Tatyana, Gorenkova Natalia, Schunk Edward, Dolgov Oleg, Bartsch Dusan

机构信息

Central Institute of Mental Health, Mannheim, Germany.

出版信息

Behav Pharmacol. 2006 May;17(3):271-87. doi: 10.1097/00008877-200605000-00008.

Abstract

A stress-induced decrease in sucrose preference in rodents is regarded as an analog of anhedonia, a key symptom of depression. We investigated the effects of citalopram, administrated via drinking water (15 mg/kg/day), in a mouse model of stress-induced anhedonia. In this model, chronic stress induces anhedonia in a subset of C57BL/6N mice, while the remaining animals do not show a hedonic deficit or other depressive-like behaviors, although they are exposed to the same stressors as the anhedonic mice. Pre-stress and post-stress treatment with citalopram counteracted the development and maintenance of anhedonia and rescued normal floating in the forced swim test, demonstrating an antidepressant-like action. During the post-stress treatment, citalopram selectively increased sucrose preference and intake on the fourth week of treatment in anhedonic mice without affecting non-anhedonic animals. Citalopram also decreased elevated water consumption in the anhedonic group. Citalopram, administered 1 week before and during a 4-week stress procedure, decreased the percentage of anhedonic mice and reduced the increase of water intake in stressed mice. This study suggests that our chronic stress paradigm can serve as a model of anhedonia, in which antidepressant treatment is selectively effective in animals with a hedonic deficit.

摘要

啮齿动物中应激诱导的蔗糖偏好降低被视为快感缺失的类似表现,而快感缺失是抑郁症的关键症状。我们研究了通过饮用水给予西酞普兰(15毫克/千克/天)对小鼠应激诱导性快感缺失模型的影响。在该模型中,慢性应激在一部分C57BL/6N小鼠中诱导出快感缺失,而其余动物尽管与快感缺失小鼠暴露于相同的应激源,但并未表现出享乐缺陷或其他抑郁样行为。应激前和应激后用西酞普兰治疗可抵消快感缺失的发展和维持,并在强迫游泳试验中恢复正常漂浮,显示出类似抗抑郁的作用。在应激后治疗期间,西酞普兰在治疗的第四周选择性地增加了快感缺失小鼠的蔗糖偏好和摄入量,而不影响非快感缺失动物。西酞普兰还降低了快感缺失组升高的饮水量。在为期4周的应激过程前1周及期间给予西酞普兰,可降低快感缺失小鼠的比例,并减少应激小鼠饮水量的增加。本研究表明,我们的慢性应激范式可作为快感缺失模型,其中抗抑郁治疗对有享乐缺陷的动物具有选择性疗效。

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