Akıllıoğlu Kübra, Köse Korkmaz Seda, Dönmez Kutlu Meltem
Çukurova University Faculty of Medicine. Department of Physiology, Department of Neurophysiology, Adana 01330, Turkey.
Çukurova University Faculty of Medicine. Department of Physiology, Department of Neurophysiology, Adana 01330, Turkey.
Behav Brain Res. 2025 Apr 12;483:115468. doi: 10.1016/j.bbr.2025.115468. Epub 2025 Feb 6.
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.
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.
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.
MK-801 administration during the neonatal period induces schizophrenia-like behaviors in adulthood, whereas low-dose caffeine can mitigate these effects.
在发育早期阶段阻断N-甲基-D-天冬氨酸（NMDA）受体被认为是一种精神分裂症样行为的模型。本研究旨在探讨咖啡因对经NMDA受体拮抗剂MK-801诱导出现精神分裂症样行为测试的成年小鼠行为的影响。
在出生后第7至10天，给Balb/c小鼠腹腔注射MK-801（0.25mg/kg，每日两次，0.1ml/10g体重）以建立精神分裂症样行为模型。在一组中，在注射MK-801后30分钟给予咖啡因（10mg/kg，每日两次，0.1ml/10g体重，腹腔注射）。在另一组中，在注射咖啡因后30分钟给予MK-801。在8至10周龄时，依次进行行为测试：旷场试验（OFT）、高架十字迷宫试验（EPM）、莫里斯水迷宫试验（MWM）和社交互动试验。
注射MK-801显著增加了焦虑样行为，并通过减少在中央区域停留的时间、进入中央区域的频率和直立频率，同时增加首次进入中央区域的潜伏期，降低了旷场试验中的探索行为。在高架十字迷宫试验中，MK-801显著减少了在开放臂停留的时间、进入开放臂的频率和开放臂的探头行为，同时增加了在封闭臂停留的时间和首次进入开放臂的潜伏期。在莫里斯水迷宫试验中，MK-801损害了学习和记忆表现。MK-801减少了社交互动。咖啡因逆转了由MK-801引起的焦虑、社交互动、学习和记忆损害。
新生儿期给予MK-801可诱导成年期出现精神分裂症样行为，而低剂量咖啡因可减轻这些影响。
