Background Memantine, a noncompetitive N-methyl-D-aspartate receptor antagonist, has been approved for use in Alzheimer’s disease, but an increasing number of studies have investigated its utility for neuropsychiatric disorders. Here, we characterized a novel compound, fluoroethylnormemtantine (FENM), which was derived from memantine with an extra Fluor in an optimized position for in vivo biomarker labeling. We sought to determine if FENM produced similar behavioral effects as memantine and/or if FENM has beneficial effects against fear, avoidance, and behavioral despair. Methods We administered saline, FENM, or memantine prior to a number of behavioral assays, including paired-pulse inhibition, open field, light dark test, forced swim test, and cued fear conditioning in male Wistar rats. Results Unlike memantine, FENM did not produce nonspecific side effects and did not alter sensorimotor gating or locomotion. FENM decreased immobility in the forced swim test. Moreover, FENM robustly facilitated fear extinction learning when administered prior to either cued fear conditioning training or tone reexposure. Conclusions These results suggest that FENM is a promising, novel compound that robustly reduces fear behavior and may be useful for further preclinical testing.

中文翻译：

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氟乙基去甲美金刚，美金刚的一种新衍生物，在没有感觉运动缺陷的情况下促进灭绝学习

背景美金刚，一种非竞争性 N-甲基-D-天冬氨酸受体拮抗剂，已被批准用于治疗阿尔茨海默病，但越来越多的研究调查了它对神经精神疾病的效用。在这里，我们表征了一种新型化合物，氟乙基去甲美金刚（FENM），它来源于美金刚，在优化的体内生物标志物标记位置具有额外的氟。我们试图确定 FENM 是否产生与美金刚相似的行为效果和/或 FENM 是否对恐惧、回避和行为绝望具有有益效果。方法 我们在进行一些行为分析之前给予生理盐水、FENM 或美金刚，包括对雄性 Wistar 大鼠的配对脉冲抑制、开放场、明暗测试、强迫游泳测试和提示恐惧条件反射。结果与美金刚不同，FENM 不会产生非特异性副作用，也不会改变感觉运动门控或运动。FENM 降低了强迫游泳测试中的不动性。此外，在提示恐惧条件训练或音调再暴露之前进行管理时，FENM 有力地促进了恐惧消退学习。结论 这些结果表明，FENM 是一种有前途的新型化合物，可有效减少恐惧行为，并可用于进一步的临床前测试。