title: Anxiolytic effects of GLYX-13 in animal models of posttraumatic stress disorder-like behavior.
abstract: In the present study, we investigated the effectiveness of GLYX-13, an NMDA receptor glycine site functional partial agonist, to alleviate the enhanced anxiety and fear response in both a mouse and rat model of stress-induced behavioral changes that might be relevant to posttraumatic stress disorder (PTSD). Studies over the last decades have suggested that the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis is one of the most consistent findings in stress-related disease. Herein, we used these animal models to further investigate the effect of GLYX-13 on the stress hormone levels and glucocorticoid receptor (GR) expression. We found that exposure to foot shock induced long-lasting behavioral deficiencies in mice, including freezing and anxiety-like behaviors, that were significantly ameliorated by the long-term administration of GLYX-13 (5 or 10 mg/kg). Our enzyme-linked immunosorbent assay results showed that long-term administration of GLYX-13 at behaviorally effective doses (5 or 10 mg/kg) significantly decreased the elevated serum levels of both corticosterone and its upstream stress hormone adrenocorticotropic hormone in rats subjected to the TDS procedure. These results suggest that GLYX-13 exerts a therapeutic effect on PTSD-like stress responding that is accompanied by (or associated with) modulation of the HPA axis, including inhibition of stress hormone levels and upregulation of hippocampal GR expression.
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing, P.R. China.
authors.forename: Zeng-Liang
authors.initials: ZL
authors.lastname: Jin
authors.affiliation: Pingdu People's Hospital, Qingdao, P.R. China.
authors.forename: Jin-Xu
authors.initials: JX
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, General Hospital of Chinese People's Armed Police Forces, Beijing, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, P.R. China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, P.R. China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Ran
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing, P.R. China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, P.R. China.
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing, P.R. China 7810906@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiong
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D014151:Anti-Anxiety Agents; D009842:Oligopeptides; D011965:Receptors, Glucocorticoid; C507283:GLYX-13 peptide; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
keywords: GLYX-13; HPA axis; Posttraumatic stress disorder; electric foot shock; glucocorticoid receptors