The effect of caffeine in a model of schizophrenia-like behavior induced by MK-801 in mice

IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES
Kübra Akıllıoğlu , Seda Köse Korkmaz , Meltem Dönmez Kutlu
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引用次数: 0

Abstract

Objective

The blockade of NMDA receptors during early developmental stages is accepted as a model for schizophrenia-like behavior. This study aimed to investigate the effects of caffeine on adult behaviors in mice subjected to tests of schizophrenia-like behaviors induced by the NMDA receptor antagonist MK-801.

Materials and methods

MK-801 (0.25 mg/kg, twice daily, 0.1 ml/10 g body weight, intraperitoneally) was administered to Balb/c mice during PND 7–10 to establish a schizophrenia-like behavior model. In one group, caffeine (10 mg/kg, twice daily, 0.1 ml/10 g body weight, intraperitoneally) was given 30 min after MK-801 administration. In another group, MK-801 was administered 30 min after caffeine injection. At 8–10 weeks of age, behavioral tests were performed sequentially: open field test (OFT), elevated plus maze test (EPM), Morris water maze test (MWM), and social interaction test.

Results

MK-801 administration significantly increased anxiety-like behaviors and decreased exploratory behavior in the OFT by reducing the time spent in the center, the frequency of center entries, and rearing frequency, while increasing the latency to the first center entry. In the EPM, MK-801 significantly decreased the time spent in the open arms, the frequency of open arm entries, and the head-dipping behavior of the open arm while increasing the time spent in the closed arms and the latency to the first open arm entry. In the MWM, MK-801 impaired learning and memory performance. MK-801 reduced social interaction. Caffeine reversed the anxiety, social interaction, learning, and memory impairments caused by MK-801.

Conclusion

MK-801 administration during the neonatal period induces schizophrenia-like behaviors in adulthood, whereas low-dose caffeine can mitigate these effects.
咖啡因对MK-801诱导的小鼠精神分裂症样行为模型的影响。
目的:早期发育阶段NMDA受体的阻断被认为是精神分裂症样行为的一种模式。本研究旨在探讨咖啡因对NMDA受体拮抗剂MK-801诱导的精神分裂症样行为小鼠成年行为的影响。材料与方法:在PND 7-10期间给Balb/c小鼠注射MK-801 (0.25mg/kg,每日2次,0.1mL/10g体重,腹腔注射),建立类精神分裂症行为模型。一组在MK-801给药30分钟后给予咖啡因(10mg/kg,每日2次,0.1mL/10g体重,腹腔注射)。在另一组中,MK-801在咖啡因注射后30分钟服用。8-10周龄时,依次进行行为学测试:开阔场测试(OFT)、高架迷宫测试(EPM)、Morris水迷宫测试(MWM)和社会互动测试。结果:MK-801通过减少在中心的停留时间、进入中心的频率和饲养频率,显著增加了OFT中的焦虑样行为和探索性行为,同时增加了第一次进入中心的延迟。在EPM中,MK-801显著减少了张开手臂的停留时间、张开手臂进入的频率和张开手臂的俯仰行为,而增加了闭合手臂的停留时间和第一次张开手臂进入的潜伏期。在MWM中,MK-801损害了学习和记忆表现。MK-801减少了社会互动。咖啡因可以逆转MK-801引起的焦虑、社交、学习和记忆障碍。结论:新生儿期给药MK-801可诱导成年期精神分裂症样行为,而低剂量咖啡因可减轻这种影响。
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来源期刊
Behavioural Brain Research
Behavioural Brain Research 医学-行为科学
CiteScore
5.60
自引率
0.00%
发文量
383
审稿时长
61 days
期刊介绍: Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.
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