1.Glutamate Receptor Antagonists Attenuate Stereotyped Behaviors via Modulating BDNF Levels in Obsessive-complusive Disorder Model Mice
Weijie WANG ; Yuchong LUO ; Dongmiao HUANG ; Chen YANG ; Jihui YUE ; Xianglan WANG ; Shenglin WEN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):475-485
ObjectiveTo explore whether fluoroethylnormemantine (FENM), an NMDA receptor antagonist, could improve compulsive-like behaviors and to investigate its underlying mechanisms in the RU24969-induced obsessive-compulsive disorder (OCD) mouse model. MethodsThirty-two mice were randomly assigned to four groups: Saline (n=8), RU24969 (n=8), RU+FENM (n=8), and FENM (n=8). Mice received FENM or an equivalent volume of saline for pre-treatment, followed by RU24969 or saline for model induction 30 minutes later. Behavioral tests were performed 1 hour after modeling, and serum samples were collected to measure the level of brain-derived neurotrophic factor (BDNF). Evans Blue dye was intravenously injected to assess dye content in brain tissue, thereby evaluating potential blood-brain barrier damage. ResultsFENM treatment significantly improved repetitive stereotyped circling behavior (F=39.850, P<0.001) and alleviated persistent motor activity (F=50.200, P<0.001) in RU24969 model mice. Additionally, FENM treatment significantly increased serum BDNF level in RU24969-induced OCD mice (F=18.930, P<0.001). ConclusionsFENM , an NMDA receptor antagonist, may alleviate compulsive behaviors in OCD mice by modulating BDNF levels , thereby exerting anti-compulsive effects. Neither the RU24969 model nor FENM treatment significantly affectes blood-brain barrier integrity.