The eventScribe Itinerary Planner system lets you effortlessly discover the content that interests you the most. Build your own personalized conference itinerary and share it with colleagues and other attendees.

When applicable, you can:

Click on icon to tweet a presentation or an exhibitor.

Click on icon to like a presentation or an exhibitor.

To get started:
Click on c icon to add the desired presentations to your plan. To finalize your plan, click on "", enter your name and email and view your itinerary by clicking on "My Plan" on the left navigation area. If you are already logged-in, the system will automatically save your changes as you make them. View Quick Start Guide

close this panel

SUBMIT FEEDBACKfeedback icon


close this panel

Technical Support

Phone: (410) 638-9239

Fax: (410) 638-6108

GoToMeeting: Meet Now!


Submit Support Ticket

close this panel

Program Number: W190      Day / Time: Wednesday, Dec 11, 5:30 PM – 7:30 PM

GLYX-13, a NMDA Receptor Glycine-Site Functional Partial Agonist, Produces Long Lasting Antidepressant-like Effects through Modulation of Long-term Synaptic Plasticity

Category: Pharmacology: pre-clinical       Sub-Category: ACNP Fellows, Members, Associate Members, and Emeritus
Jeffrey Burgdorf – Northwestern University, Evanston, Illinois
Xiao-lei Zhang – New York Medical College, Valhalla, New York
Amanda Gross – Naurex, Inc, Evanston, Illinois
Roger Kroes – Northwestern University, Evanston, Illinois
Patric Stanton – New York Medical College, Valhalla, New York
J. David Leander – Naurex, Inc, Evanston, Illinois
Ronald M. Burch – Naurex, Inc, Morris, Connecticut
Joseph Moskal – Northwestern University, Evanston, Illinois
J. Burgdorf, Part 1: Naurex ,Inc, Part 2: Naurex ,Inc, Part 3: Naurex ,Inc; X. Zhang, Nothing to Disclose; A. Gross, Part 5: Naurex, Inc; R. Kroes , Part 1: Naurex, Inc, Part 2: Naurex, Inc, Part 4: Naurex, Inc; P. Stanton , Part 1: Naurex, Inc, Part 2: Naurex, Inc, Part 4: Naurex, Inc; J. Leander, Part 1: Naurex, Inc, AgeneBio, Nektar, and CoLucid; R. Burch, Part 5: Naurex, Inc; J. Moskal, Part 1: Naurex, Inc, Part 2: Naurex, Inc, Part 3: Naurex, Inc

Background: GLYX-13, a glycine-site functional partial agonist at the NMDAR, is currently in phase II clinical development as an adjunctive therapy for major depressive disorder ( identifier NCT01684163). GLYX-13 has been shown to: a) preferentially enhance conductance of NR2B-containing NMDARs at rat Schaffer collateral-CA1 synapses in vitro; b) enhance the magnitude of long-term potentiation (LTP) of synaptic transmission while simultaneously reducing that of long-term depression (LTD), which differentiates GLYX-13 from other NMDAR modulators such as D-cycloserine. In animal studies, GLYX-13 has been shown to: a) enhance performance in several hippocampus-dependent learning tasks in both young adult and learning-impaired aged rats;  and d) produce an antidepressant-like effects in a variety of models without ketamine-like dissociative, addictive or sedative side effects.

Chronic Unpredictable Stress (CUS) Procedure:  Male Sprague-Dawley (SD) rats (2-3 Months old) received 21 days of CUS: 9 different CUS stressors were used (2 stressors per day). Animals in the CUS groups received a single optimal dose of GLYX-13 (3 mg/kg IV; n = 10) previously shown to produce a robust antidepressant-like response or sterile saline vehicle ( n = 10).  Porsolt Test:  Animals were placed in a 46 cm tall x 20 cm in diameter clear glass tube filled to 30 cm with tap water (23 ± 1 °C) for 15 min on the first day (habituation) and 5 min on the subsequent test days (1 hr, 24 hrs, 1 week, 2 weeks post-dosing).  Sucrose Preference Test:  Rats were exposed to a palatable sucrose solution (1%; Sigma, USA) for 48 hours, followed by 4 hours of water deprivation and a 1 hour exposure to two identical bottles, one filled with sucrose solution and the other with tap water.  Novelty Induced Hypophagia (NIH) Test:  Animals were food deprived on the night before testing, and lab chow was placed into the center chamber of the open field (40 x 40 x20 cm) for 10 min under dim-red lighting. Ultrasonic Vocalization (USV) Test:  Animals received 3 min of heterospecific rough-and-tumble play consisting of alternating 15 s blocks of heterospecific play and 15 s of no-stimulation.  Microarray Analyses:  Triplicate microarray analyses were performed using the medial prefrontal cortex (MPFC) isolated from individual non-CUS treated animals injected with GLYX- 13 (3 mg/kg IV), or saline vehicle (1 ml/kg IV). Individual 45-mer oligonucleotides complementary to sequences of 1178 cloned rat CNS mRNAs were synthesized on a PolyPlex™ 96-well oligonucleotide synthesizer (GeneMachines®, USA) and spotted in triplicate onto epoxy coated slides (Telechem, USA) using an OmniGrid™ robotic microarrayer (GeneMachines®). Hippocampal Slice Electrophysiology:  Hippocampal slices were prepared from adult male SD rats 24 hours after a single injection of GLYX-13 (3 mg/kg IV), ketamine (10 mg/kg IV) or vehicle. LTP at Schaffer collateral-CA1 synapses was measured in response to three submaximal bouts of high-frequency Schaffer collateral stimulation (2x100Hz/800ms). 

A single IV dose of GLYX-13 produced a long-lasting antidepressant-like effect in the Porsolt, sucrose preference, and NIH tests in rats exposed to CUS.  GLYX-13 also produced a long-lasting antidepressant-like effect in the USVs test and increased positive emotional learning in rats exposed to CUS. The AMPA / kainate receptor antagonist NBQX, 24 hrs post-dosing, occluded the antidepressant-like effect of GLYX-13 in the Porsolt test.  GLYX-13, 24 hrs and 2 weeks post-dosing, showed enrichment in LTP- and LTD-associated genes in the medial prefrontal cortex as measured by microarray.  GLYX-13 metaplasticly enhances LTP 24 h and 1 week following a single dose, and persistently enhances LTP following multiple bi-weekly doses.

We have hypothesized that the long-lasting antidepressant effects of GLYX-13 are due to metaplastic enhancement in long-term activity-dependent synaptic plasticity.  Based on the results reported here we suggest that the long-lasting antidepressant-like effects of GLYX-13 are due at least in part to metaplasticity mechanisms associated with NMDAR-triggered induction of LTP.  The induction/upregulation of LTD-associated transcripts at 1 hr by GLYX-13 may produce a shift in the threshold for future synaptic plasticity processes.  This shift may initially favor LTD and be associated with a more sustained rebound that persistently favors future LTP since it is well established that the thresholds for LTD and LTP are plastic. 


"eventScribe", the eventScribe logo, "CadmiumCD", and the CadmiumCD logo are trademarks of CadmiumCD LLC, and may not be copied, imitated or used, in whole or in part, without prior written permission from CadmiumCD. The appearance of these proceedings, customized graphics that are unique to these proceedings, and customized scripts are the service mark, trademark and/or trade dress of CadmiumCD and may not be copied, imitated or used, in whole or in part, without prior written notification. All other trademarks, slogans, company names or logos are the property of their respective owners. Reference to any products, services, processes or other information, by trade name, trademark, manufacturer, owner, or otherwise does not constitute or imply endorsement, sponsorship, or recommendation thereof by CadmiumCD.

As a user you may provide CadmiumCD with feedback. Any ideas or suggestions you provide through any feedback mechanisms on these proceedings may be used by CadmiumCD, at our sole discretion, including future modifications to the eventScribe product. You hereby grant to CadmiumCD and our assigns a perpetual, worldwide, fully transferable, sublicensable, irrevocable, royalty free license to use, reproduce, modify, create derivative works from, distribute, and display the feedback in any manner and for any purpose.

© 2014 CadmiumCD