Melatonin attenuated the behavioral despair induced by acute neurogenic stress through blockade of N-methyl D-aspartate receptors in mice

Arwin Hajmirzaeyian; Mohsen Chamanara; Amir Rashidian; Saied Shakyba; Ehsan Nassireslami; Reza Akhavan-Sigari

doi:10.1016/j.heliyon.2021.e05900

Melatonin attenuated the behavioral despair induced by acute neurogenic stress through blockade of N-methyl D-aspartate receptors in mice

Heliyon. 2021 Jan 11;7(1):e05900. doi: 10.1016/j.heliyon.2021.e05900. eCollection 2021 Jan.

Authors

Arwin Hajmirzaeyian^{1

2}, Mohsen Chamanara², Amir Rashidian¹, Saied Shakyba^{1

2}, Ehsan Nassireslami², Reza Akhavan-Sigari³

Affiliations

¹ Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
² Department of Pharmacology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran.
³ Department of Neurosurgery, University Medical Center Tuebingen, Germany.

Abstract

It has been well documented that administration of melatonin could reveal antidepressant-like effect in rodents. However, the protective effect of melatonin on stress-induced depression/anxiety and its underlying mechanism is yet to be understood. In this regard, in the current study, acute foot-shock stress (FSS) was used to evaluate the antidepressant-like effect of melatonin on neurogenic stress-induced depression in mice. Behavioral evaluation was done by using the forced swimming test (FST) and Open-field test (OFT). Melatonin, MK-801, and ketamine (NMDA receptor antagonists), and NMDA (NMDA receptor agonist) were used to elucidate any association between melatonin and NMDA pathway in behavioral despair induced by acute-FSS. Applying acute-FSS to mice significantly induced depressant-like behavior in FST without any significant impact on locomotor activity in the OFT. We observed that melatonin (dose-dependently) significantly improved the depressant-like effect of FSS, but it did not impact the locomotion in animals. Acute injection of MK-801 at sub-effective doses (0.01 mg/kg) or ketamine (0.1 mg/kg) potentiated the antidepressant-like effect of a sub-effective dose of melatonin. However, the sub-effective dose of NMDA (30 mg/kg) abolished the protective effect of melatonin on the behavioral profile of stressed animals. Our results could reflect the antidepressant-like effect of melatonin on neurogenic stress-induced depressive behaviors in mice. Also, our results showed that NMDA receptors could be involved in the antidepressant-like effect of melatonin.

Keywords: Acute foot shock stress; Behavioral despair; Melatonin; Mice; NMDA receptor.