Investigation of antidepressant-like and anxiolytic-like actions and cognitive and motor side effects of four N-methyl-D-aspartate receptor antagonists in mice

Research output: Contribution to journalJournal articleResearchpeer-review

Louise Konradsen Refsgaard, Darryl S Pickering, Jesper Andreasen T.

Evidence suggests that N-methyl-D-aspartate receptor (NMDAR) antagonists could be efficacious in treating depression and anxiety, but side effects constitute a challenge. This study evaluated the antidepressant-like and
anxiolytic-like actions, and cognitive and motor side effects of four NMDAR antagonists. MK-801, ketamine, S-ketamine, RO 25-6981 and the positive control, citalopram, were tested for antidepressant-like and anxiolytic-like effects in mice using the forced-swim test, the elevated zero maze and the novelty-induced hypophagia test. Side effects were assessed using a locomotor activity test, the modified Y-maze and the rotarod test. All compounds increased swim distance in the forced-swim test. In the elevated zero maze, the GluN2B subtype-selective RO 25-6981 affected none of the measured parameters, whereas all other compounds showed anxiolytic-like effects. In the novelty-induced hypophagia test, citalopram and MK-801 showed anxiogenic-like action. All NMDAR antagonists induced hyperactivity. The high doses of ketamine and MK-801 impaired performance in the modified Y-maze test, whereas S-ketamine and RO 25-6891 showed no effects in this test. Only MK-801 impaired rotarod performance. The study supports that NMDARs could be a possible therapeutic target for treating depression and anxiety. However,
selective antagonism of GluN2B subunit-containing NMDARs showed no effect on anxiety-like behaviours in this study.
Original languageEnglish
JournalBehavioural Pharmacology
Volume28
Issue number1
Pages (from-to)37-47
Number of pages11
ISSN0955-8810
DOIs
Publication statusPublished - 1 Feb 2017

ID: 164572584