title: D-serine enhances fear extinction by increasing GluA2-containing AMPA receptor endocytosis.
abstract: Activation of the N-methyl-D-aspartate receptor (NMDAR) glycine site has been shown to enhance memory extinction in physiological and pathological conditions. In the current study, we examined the effects of D-serine, an endogenous NMDAR glycine site agonist, on fear extinction and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) endocytosis in the hippocampus during the process of fear extinction. In inhibitory avoidance task, systemic administration of D-serine (800 mg/kg, i.p.) significantly accelerated memory extinction. The Western blot analyses showed that the acceleration of memory extinction was accompanied by an increase in postsynaptic AMPAR endocytosis in the hippocampus. Furthermore, the application of a synthetic peptide Tat-GluA23Y (3.0 μmol/kg, i.p.) that interferes with the endocytosis of AMPARs succeeded in preventing the enhancement of fear extinction and AMPAR endocytosis induced by D-serine. These results suggest that d-serine might enhance fear extinction through increasing GluA2-containing AMPA receptor endocytosis, and that d-serine may be a potential therapeutic agent against learning and memory disorders.
authors.affiliation: Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China. Electronic address: zfdong@cqmu.edu.cn.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects*; D009483:Neuropsychological Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D012694:Serine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018091:Receptors, AMPA; D012694:Serine; C104722:glutamate receptor ionotropic, AMPA 2
keywords: AMPA receptors; Extinction; d-Serine