对α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体的正向调节可不同程度地改变三周以下和三周以上幼鼠的空间学习和记忆。

IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES
Behavioural Pharmacology Pub Date : 2024-04-01 Epub Date: 2024-03-06 DOI:10.1097/FBP.0000000000000764
Nicholas R Mill, Richard H Ogoe, Nazanin Valibeigi, Diyi Chen, Carmen L Kimbal, Stanley J Yoon, Shaunak Ganju, Josue A Perdomo, Anjali Sardana, Daniel G McHail, Diego A Gonzalez, Theodore C Dumas
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引用次数: 0

摘要

啮齿类动物在出生后第三周结束时,在各种需要根据空间环境进行导航的任务测试中表现出显著的进步。虽然海马功能的改变至少部分支持了这种认知能力的提高,但生理学解释仍然不完整。此前,我们发现幼年大鼠海马谷氨酸能α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体的发育改变与对称Y迷宫中更成熟的自发交替行为有关。此外,AMPA受体的一种正异位调节剂能使未成熟大鼠的交替率达到年长动物的水平,这表明兴奋性突触对海马成熟的限制。随后,我们对幼年大鼠的巴恩斯迷宫进行了验证,以测试 AMPA 受体正向调节对目标定向空间记忆任务的影响。在此,我们报告了 AMPA 受体调节剂 CX614 对巴恩斯迷宫空间学习和记忆的影响。与我们之前的报告类似,3周龄以上的动物与3周龄以下的动物相比,在学习和记忆表现参数上都有显著改善。中等剂量的 CX614 能使未成熟的动物更直接地移动到目标位置,但仅在训练 1 天后才能实现。在第二天的给药训练中,或在第二天训练后不给药的记忆探测试验中,都能观察到这种性能的提高。高剂量会造成更多的搜索错误,尤其是在更成熟的动物身上。总体而言,CX614在目标导向的空间记忆任务中对未成熟大鼠的表现略有益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Positive modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors differentially alters spatial learning and memory in juvenile rats younger and older than three weeks.

Remarkable performance improvements occur at the end of the third postnatal week in rodents tested in various tasks that require navigation according to spatial context. While alterations in hippocampal function at least partially subserve this cognitive advancement, physiological explanations remain incomplete. Previously, we discovered that developmental modifications to hippocampal glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in juvenile rats was related to more mature spontaneous alternation behavior in a symmetrical Y-maze. Moreover, a positive allosteric modulator of AMPA receptors enabled immature rats to alternate at rates seen in older animals, suggesting an excitatory synaptic limitation to hippocampal maturation. We then validated the Barnes maze for juvenile rats in order to test the effects of positive AMPA receptor modulation on a goal-directed spatial memory task. Here we report the effects of the AMPA receptor modulator, CX614, on spatial learning and memory in the Barnes maze. Similar to our prior report, animals just over 3 weeks of age display substantial improvements in learning and memory performance parameters compared to animals just under 3 weeks of age. A moderate dose of CX614 enabled immature animals to move more directly to the goal location, but only after 1 day of training. This performance improvement was observed on the second day of training with drug delivery or during a memory probe trial performed without drug delivery after the second day of training. Higher doses created more search errors, especially in more mature animals. Overall, CX614 provided modest performance benefits for immature rats in a goal-directed spatial memory task.

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来源期刊
Behavioural Pharmacology
Behavioural Pharmacology 医学-行为科学
CiteScore
3.40
自引率
0.00%
发文量
84
审稿时长
6-12 weeks
期刊介绍: Behavioural Pharmacology accepts original full and short research reports in diverse areas ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Suitable topics include drug, chemical and hormonal effects on behaviour, the neurochemical mechanisms under-lying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are welcome; however, studies reporting neurochemical data should have a predominantly behavioural focus, and human studies should not consist exclusively of clinical trials or case reports. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems. Papers making a significant theoretical contribution are particularly welcome and, where possible and merited, space is made available for authors to explore fully the theoretical implications of their findings. Reviews of an area of the literature or at an appropriate stage in the development of an author’s own work are welcome. Commentaries in areas of current interest are also considered for publication, as are Reviews and Commentaries in areas outside behavioural pharmacology, but of importance and interest to behavioural pharmacologists. Behavioural Pharmacology publishes frequent Special Issues on current hot topics. The editors welcome correspondence about whether a paper in preparation might be suitable for inclusion in a Special Issue.
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