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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Investigation of antidepressant-like and anxiolytic-like actions and cognitive and motor side effects of four N-methyl-D-aspartate receptor antagonists in mice. / Refsgaard, Louise Konradsen; Pickering, Darryl S; Andreasen T., Jesper.
In: Behavioural Pharmacology, Vol. 28, No. 1, 01.02.2017, p. 37-47.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Investigation of antidepressant-like and anxiolytic-like actions and cognitive and motor side effects of four N-methyl-D-aspartate receptor antagonists in mice
AU - Refsgaard, Louise Konradsen
AU - Pickering, Darryl S
AU - Andreasen T., Jesper
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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 andanxiolytic-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.
AB - 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 andanxiolytic-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.
U2 - 10.1097/FBP.0000000000000266
DO - 10.1097/FBP.0000000000000266
M3 - Journal article
C2 - 27740963
VL - 28
SP - 37
EP - 47
JO - Behavioural Pharmacology
JF - Behavioural Pharmacology
SN - 0955-8810
IS - 1
ER -
ID: 164572584