Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Effects of D-amino acid oxidase inhibition on memory performance and long-term potentiation in vivo

Tools
- Tools
+ Tools

Hopkins, Seth C., Campbell, Una C., Heffernan, Michele L. R., Spear, Kerry L., Jeggo, Ross D., Spanswick, David C., Varney, Mark A. and Large, Thomas H. (2013) Effects of D-amino acid oxidase inhibition on memory performance and long-term potentiation in vivo. Pharmacology Research & Perspectives, Volume 1 (Number 1). doi:10.1002/prp2.7

[img]
Preview
Text
WRAP_Spanswick_prp27.pdf - Published Version
Available under License Creative Commons Attribution.

Download (1476Kb) | Preview
Official URL: http://dx.doi.org/10.1002/prp2.7

Request Changes to record.

Abstract

N-methyl-d-aspartate receptor (NMDAR) activation can initiate changes in synaptic strength, evident as long-term potentiation (LTP), and is a key molecular correlate of memory formation. Inhibition of d-amino acid oxidase (DAAO) may increase NMDAR activity by regulating d-serine concentrations, but which neuronal and behavioral effects are influenced by DAAO inhibition remain elusive. In anesthetized rats, extracellular field excitatory postsynaptic potentials (fEPSPs) were recorded before and after a theta frequency burst stimulation (TBS) of the Schaffer collateral pathway of the CA1 region in the hippocampus. Memory performance was assessed after training with tests of contextual fear conditioning (FC, mice) and novel object recognition (NOR, rats). Oral administration of 3, 10, and 30 mg/kg 4H-furo[3,2-b]pyrrole-5-carboxylic acid (SUN) produced dose-related and steady increases of cerebellum d-serine in rats and mice, indicative of lasting inhibition of central DAAO. SUN administered 2 h prior to training improved contextual fear conditioning in mice and novel object recognition memory in rats when tested 24 h after training. In anesthetized rats, LTP was established proportional to the number of TBS trains. d-cycloserine (DCS) was used to identify a submaximal level of LTP (5× TBS) that responded to NMDA receptor activation; SUN administered at 10 mg/kg 3–4 h prior to testing similarly increased in vivo LTP levels compared to vehicle control animals. Interestingly, in vivo administration of DCS also increased brain d-serine concentrations. These results indicate that DAAO inhibition increased NMDAR-related synaptic plasticity during phases of post training memory consolidation to improve memory performance in hippocampal-dependent behavioral tests.

Item Type: Journal Article
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Cognition , Memory , Hippocampus (Brain)
Journal or Publication Title: Pharmacology Research & Perspectives
Publisher: John Wiley & Sons Ltd.
ISSN: 2052-1707
Official Date: 1 October 2013
Dates:
DateEvent
1 October 2013["eprint_fieldopt_dates_date_type_available" not defined]
Volume: Volume 1
Number: Number 1
DOI: 10.1002/prp2.7
Status: Peer Reviewed
Publication Status: Published
Funder: Sunovion Pharmaceuticals Inc.

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us