학술논문
Fluoroethylnormemantine, A Novel Derivative of Memantine, Facilitates Extinction Learning Without Sensorimotor Deficits
REGULAR RESEARCH ARTICLE
REGULAR RESEARCH ARTICLE
Document Type
Report
Author
Source
International Journal of Neuropsychopharmacology. June 2021, Vol. 24 Issue 6, p519, 25 p.
Subject
Language
English
ISSN
1461-1457
Abstract
Introduction N-methyl-D-aspartate (NMDA) receptor (NMDAR) function has been increasingly implicated in the pathophysiology of neuropsychiatric diseases, including mood disorders and Alzheimer's disease (AD) (Paul, 1997; Ravindran and Stein, 2009; Barkus [...]
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, fuoroethylnormemtantine (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. Key Words: FENM, extinction learning, cued fear conditioning, PTSD, NMDAR antagonist
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, fuoroethylnormemtantine (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. Key Words: FENM, extinction learning, cued fear conditioning, PTSD, NMDAR antagonist