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用于临床前研究的智能笼系统中的时间感知测试:抑郁症与血清素调节的关联

Time Perception Test in IntelliCage System for Preclinical Study: Linking Depression and Serotonergic Modulation.

作者信息

Sysoeva Olga, Akhmirov Rauf, Zaichenko Maria, Lazarenko Ivan, Rebik Anastasiya, Broshevitskaja Nadezhda, Midzyanovskaya Inna, Smirnov Kirill

机构信息

Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117465 Moscow, Russia.

Center for Cognitive Sciences, Sirius University of Science and Technology, Olimpiyskiy Ave. b.1, 354340 Sirius, Russia.

出版信息

Diagnostics (Basel). 2025 Jan 10;15(2):151. doi: 10.3390/diagnostics15020151.

DOI:10.3390/diagnostics15020151
PMID:39857035
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11764329/
Abstract

The link between serotonergic modulation and depression is under debate; however, serotonin reuptake inhibitors (SRIs) are still the first-choice medicine in this condition. Disturbances in time perception are also reported in depression with one of the behavioral schedules used to study interval timing, differential-reinforcement-learning-of-low-rate, having been shown to have high predictive validity for an antidepressant effect. Here, we introduce an IntelliCage research protocol of an interval bisection task that allows more ecologically valid and less time-consuming rodent examination and provides an example of its use to confirm the previously reported acute effect of an SRI, clomipramine, on interval timing (increase in bisection point, D50). Wistar male rats ( = 25, five groups of 5-8) were trained in the IntelliCage to discriminate between short (1 s) and long (4 s) LED light stimuli by nose poking at the corresponding (left/right) side of the IntelliCage chamber to obtain a drink. When 80% of correct responses were reached, the intermediate durations of 1.7, 2.5, and 3.3 s were introduced. The number of left/right choices for each stimulus and interval timing parameters (bisection point, D50, and timing precision), derived from them, were compared after saline and clomipramine (7 mg/kg, i.p) intraperitoneal administration. : Rats successfully learned the task within about a week of training. The slightly increased D50 after clomipramine confirmed previous studies. The introduced protocol has potential to be applicable to preclinical research on depression and potentially other psychopathology, where time perception can be disturbed.

摘要

血清素调节与抑郁症之间的联系仍存在争议;然而,血清素再摄取抑制剂(SRIs)仍是治疗这种疾病的首选药物。抑郁症患者也存在时间感知障碍,用于研究间隔计时的行为程序之一——低比率差异强化学习,已被证明对抗抑郁效果具有较高的预测效度。在此,我们介绍一种间隔二等分任务的智能笼研究方案,该方案能使啮齿动物检查更符合生态学效度且耗时更少,并提供了一个使用该方案的例子,以证实先前报道的SRI氯米帕明对间隔计时的急性作用(二等分点增加,D50)。将25只雄性Wistar大鼠(分为5组,每组5 - 8只)置于智能笼中训练,通过在智能笼腔室相应的(左/右)侧戳鼻以获得饮品,从而区分短(1秒)和长(4秒)的LED光刺激。当正确反应达到80%时,引入1.7、2.5和3.3秒的中间时长。在腹腔注射生理盐水和氯米帕明(7毫克/千克)后,比较每种刺激的左右选择数量以及从中得出的间隔计时参数(二等分点、D50和计时精度)。结果表明:大鼠在大约一周的训练内成功学会了该任务。氯米帕明给药后D50略有增加,证实了先前的研究。所引入的方案有可能应用于抑郁症以及其他可能存在时间感知障碍的精神病理学的临床前研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/11764329/66da3624ebd9/diagnostics-15-00151-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/11764329/41d252b70b72/diagnostics-15-00151-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/11764329/66da3624ebd9/diagnostics-15-00151-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/11764329/41d252b70b72/diagnostics-15-00151-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/11764329/66da3624ebd9/diagnostics-15-00151-g002.jpg

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本文引用的文献

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Int J Mol Sci. 2024 Dec 11;25(24):13305. doi: 10.3390/ijms252413305.
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IntelliCage: the development and perspectives of a mouse- and user-friendly automated behavioral test system.智能鼠笼:一种对小鼠和用户友好的自动化行为测试系统的开发与前景
Front Behav Neurosci. 2024 Jan 3;17:1270538. doi: 10.3389/fnbeh.2023.1270538. eCollection 2023.
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Acute but not long-lasting antidepressant-like effect of psilocybin in differential reinforcement of low-rate 72 schedule in rats.
裸盖菇素对大鼠低频率 72 时距强化程序的急性但非持久抗抑郁样效应。
J Psychopharmacol. 2023 Nov;37(11):1149-1156. doi: 10.1177/02698811231205692. Epub 2023 Oct 16.
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Lower loss rate of serotonergically modulated neuronal accumulator for time in patients with major depressive disorder.降低重性抑郁障碍患者中 5-羟色胺能调制神经元累加器的时间损失率。
J Psychiatr Res. 2023 Sep;165:345-351. doi: 10.1016/j.jpsychires.2023.08.005. Epub 2023 Aug 9.
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Interval timing relative to response inhibition in the differential reinforcement of low-rate responding in normally developing young adults.正常发育的年轻成年人在低频反应中进行区分性强化时,反应抑制的间隔计时。
Sci Rep. 2023 Jul 24;13(1):11977. doi: 10.1038/s41598-023-39160-z.
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Effects of ketamine optical isomers, fluoxetine and naloxone on timing in differential reinforcement of low-rate response (DRL) 72-s task in rats.氯胺酮光学异构体、氟西汀和纳洛酮对大鼠低速率反应(DRL)72秒任务中定时的影响。
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