TY - JOUR T1 - d-serine enhances extinction of auditory cued fear conditioning via ERK1/2 phosphorylation in mice. AU - Matsuda,Shingo, AU - Matsuzawa,Daisuke, AU - Nakazawa,Ken, AU - Sutoh,Chihiro, AU - Ohtsuka,Hiroyuki, AU - Ishii,Daisuke, AU - Tomizawa,Haruna, AU - Iyo,Masaomi, AU - Shimizu,Eiji, Y1 - 2010/04/21/ PY - 2009/10/19/received PY - 2010/04/01/revised PY - 2010/04/14/accepted PY - 2010/4/27/entrez PY - 2010/4/27/pubmed PY - 2010/11/3/medline SP - 895 EP - 902 JF - Progress in neuro-psychopharmacology & biological psychiatry JO - Prog Neuropsychopharmacol Biol Psychiatry VL - 34 IS - 6 N2 - Several lines of evidence suggest that the N-methyl-D-aspartate (NMDA) receptor plays a significant role in fear conditioning and extinction. However, our knowledge of the role of D-serine, an endogenous ligand for the glycine site of the NMDA receptor, in fear extinction is quite limited compared to that of D-cycloserine, an exogenous partial agonist for the same site. In the current study, we examined the effects of D-serine on fear extinction and phosphorylation of extracellular signal-regulated kinase (ERK) in the hippocampus, basolateral amygdala (BLA), and medial prefrontal cortex (mPFC) during the process of fear extinction. Systemic administrations of D-serine (2.7 g/kg, i.p.) with or without the ERK inhibitor SL327 (30 mg/kg, i.p.) to C57BL/6J mice were performed before fear extinction in a cued fear conditioning and extinction paradigm. Cytosolic and nuclear ERK 1/2 phosphorylation in the hippocampus, BLA, and mPFC were measured 1h after extinction (E1h), 24h after extinction (E24h), and 1h after recall (R1h) by Western blotting. We found that D-serine enhanced the extinction of fear memory, and the effects of D-serine were reduced by the ERK phosphorylation inhibitor SL327. The Western blot analyses showed that D-serine significantly increased cytosolic ERK 2 phosphorylation at E1h in the hippocampus and cytosolic ERK 1/2 phosphorylation at R1h in the BLA. The present study suggested that D-serine might enhance fear extinction through NMDA receptor-induced ERK signaling in mice, and that D-serine has potential clinical importance for the treatment of anxiety disorders. SN - 1878-4216 UR - https://www.unboundmedicine.com/medline/citation/20416352/d_serine_enhances_extinction_of_auditory_cued_fear_conditioning_via_ERK1/2_phosphorylation_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-5846(10)00142-9 DB - PRIME DP - Unbound Medicine ER -