Investigation of antidepressant-like and anxiolytic-like actions and cognitive and motor side effects of four N-methyl-D-aspartate receptor antagonists in mice.
| Title: | Investigation of antidepressant-like and anxiolytic-like actions and cognitive and motor side effects of four N-methyl-D-aspartate receptor antagonists in mice. |
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| Authors: | Refsgaard LK; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Pickering DS; Andreasen JT |
| Source: | Behavioural pharmacology [Behav Pharmacol] 2017 Feb; Vol. 28 (1), pp. 37-47. |
| Publication Type: | Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Lippincott Williams and Wilkins Country of Publication: England NLM ID: 9013016 Publication Model: Print Cited Medium: Internet ISSN: 1473-5849 (Electronic) Linking ISSN: 09558810 NLM ISO Abbreviation: Behav Pharmacol Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : Lippincott Williams and Wilkins; Original Publication: London : Clinical Neuroscience Publishers |
| MeSH Terms: | Anti-Anxiety Agents/*pharmacology ; Antidepressive Agents/*pharmacology ; Depression/*drug therapy ; Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors; Anti-Anxiety Agents/administration & dosage ; Anti-Anxiety Agents/toxicity ; Antidepressive Agents/administration & dosage ; Antidepressive Agents/toxicity ; Anxiety/drug therapy ; Behavior, Animal/drug effects ; Cognition/drug effects ; Maze Learning/drug effects ; Motor Activity/drug effects ; Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Mice ; Swimming |
| Abstract: | 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. |
| Substance Nomenclature: | 0 (Anti-Anxiety Agents); 0 (Antidepressive Agents); 0 (NR2B NMDA receptor); 0 (Receptors, N-Methyl-D-Aspartate) |
| Entry Date(s): | Date Created: 20161015 Date Completed: 20180108 Latest Revision: 20180228 |
| Update Code: | 20260130 |
| DOI: | 10.1097/FBP.0000000000000266 |
| PMID: | 27740963 |
| Database: | MEDLINE |
Comparative Study; Journal Article; Research Support, Non-U.S. Gov't