Repository of Research and Investigative Information

Repository of Research and Investigative Information

Baqiyatallah University of Medical Sciences

NMDA receptor antagonists augment antidepressant-like effects of lithium in the mouse forced swimming test

(2010) NMDA receptor antagonists augment antidepressant-like effects of lithium in the mouse forced swimming test. Journal of Psychopharmacology. pp. 585-594. ISSN 0269-8811

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Abstract

Although there is evidence of the involvement of N-methyl-D-aspartate receptors (NMDAR) in the action of lithium, its role in the antidepressant effects of lithium in a behavioural model remains unclear. In this study, we evaluated the effects of NMDAR antagonists on the antidepressant-like effects of lithium in the mouse forced swimming test. Lithium (30 and 100 mg/kg, i.p.) significantly (P < 0.01) reduced the immobility times of mice, whereas at lower doses (5 and 10 mg/kg) had no effect. NMDA antagonists ketamine (2 and 5 mg/kg, i.p.), MK-801 (0.1 and 0.25 mg/kg, i.p.) and ifenprodil (1 and 3 mg/kg, i.p.) significantly (P < 0.05) decreased the immobility time. Lower doses of ketamine (0.5 and 1 mg/kg), MK-801 (0.01 and 0.05 mg/kg) and ifenprodil (0.1 and 0.5 mg/kg) had no effect. Combined treatment of subeffective doses of lithium (10 mg/kg) and ketamine (1 mg/kg), MK-801 (0.05 mg/kg) or ifenprodil (0.5 mg/kg) robustly (P < 0.001) exerted an antidepressant-like effect. The noneffective dose of a NMDA agonist (NMDA, 75 mg/kg, i.p.) prevented the antidepressant-like effect of lithium (30 mg/kg). None of the drugs at subactive doses or in combination with lithium had significant effect on the locomotor activity in the open field test. We for the first time suggested a role for NMDAR signalling in the antidepressant-like effects of lithium, providing a new approach for treatment of depression.

Item Type: Article
Keywords: depression forced swimming test ifenprodil ketamine lithium mice MK-801 NMDA N-methyl-D-aspartate receptor antagonists d-aspartate receptor major depressive disorder olfactory bulbectomized rat cerebral-cortex slices bipolar disorder learned helplessness tyrosine phosphorylation exhibit antidepressant behavioral despair glutamate release Neurosciences & Neurology Pharmacology & Pharmacy Psychiatry
Divisions:
Page Range: pp. 585-594
Journal or Publication Title: Journal of Psychopharmacology
Journal Index: ISI
Volume: 24
Number: 4
Identification Number: https://doi.org/10.1177/0269881109104845
ISSN: 0269-8811
Depositing User: مهندس مهدی شریفی
URI: http://eprints.bmsu.ac.ir/id/eprint/6748

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