Continuous home cage monitoring of activity and sleep in mice during repeated paroxetine treatment and discontinuation.

Continuous home cage monitoring of activity and sleep in mice during repeated paroxetine treatment and discontinuation.
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DOI:
10.1007/s00213-023-06442-3
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发表时间:
2023-11
期刊:
影响因子:
3.4
通讯作者:
Peirson SN
Peirson SN
中科院分区:
医学3区
文献类型:
--
作者:
Collins HM;Pinacho R;Tam SKE;Sharp T;Bannerman DM;Peirson SN

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无创家庭笼监测正在成为评估实验性干预对小鼠行为影响的一种有价值的工具。这些技术可能被证明有用的一个领域是反复选择性血清素再摄取抑制剂(SSRI)治疗和停药的研究。SSRI停药综合征是一种研究不足的情况,包括治疗停止后出现的睡眠障碍。我们使用被动红外(PIR)监测研究了在重复使用SSRI类药物帕罗西汀和停药期间小鼠活动、睡眠和昼夜节律的变化。雄性小鼠注射帕罗西汀(10mg /kg/天,s.c) 12天,然后换成生理盐水注射13天,并与自始至终接受生理盐水注射的小鼠进行比较。使用连续开放小鼠活动和睡眠状态表型(COMPASS)系统对小鼠进行连续跟踪。反复的帕罗西汀治疗减少了活动,增加了黑暗阶段的行为定义睡眠。这些影响在帕罗西汀停药后24小时内恢复到盐分控制水平,但也有证据表明,在停药后长达一周的黑暗期睡眠时间延长。这项研究提供了第一个例子,说明如何使用连续的无创家庭笼监测来检测药物治疗期间和之后小鼠活动和睡眠的客观行为变化。这些数据表明,帕罗西汀的作用在停药后很快就会逆转,但发现睡眠持续时间出现了紧急变化,这可以作为未来临床前研究的生物标志物,以预防或减少SSRI停药症状。在线版本包含补充材料,可在10.1007/s00213-023-06442-3获得。
Non-invasive home cage monitoring is emerging as a valuable tool to assess the effects of experimental interventions on mouse behaviour. A field in which these techniques may prove useful is the study of repeated selective serotonin reuptake inhibitor (SSRI) treatment and discontinuation. SSRI discontinuation syndrome is an under-researched condition that includes the emergence of sleep disturbances following treatment cessation. We used passive infrared (PIR) monitoring to investigate changes in activity, sleep, and circadian rhythms during repeated treatment with the SSRI paroxetine and its discontinuation in mice. Male mice received paroxetine (10 mg/kg/day, s.c.) for 12 days, then were swapped to saline injections for a 13 day discontinuation period and compared to mice that received saline injections throughout. Mice were continuously tracked using the Continuous Open Mouse Phenotyping of Activity and Sleep Status (COMPASS) system. Repeated paroxetine treatment reduced activity and increased behaviourally-defined sleep in the dark phase. These effects recovered to saline-control levels within 24 h of paroxetine cessation, yet there was also evidence of a lengthening of sleep bouts in the dark phase for up to a week following discontinuation. This study provides the first example of how continuous non-invasive home cage monitoring can be used to detect objective behavioural changes in activity and sleep during and after drug treatment in mice. These data suggest that effects of paroxetine administration reversed soon after its discontinuation but identified an emergent change in sleep bout duration, which could be used as a biomarker in future preclinical studies to prevent or minimise SSRI discontinuation symptoms. The online version contains supplementary material available at 10.1007/s00213-023-06442-3.
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