Abstract

ANTIDEPRESSANT-LIKE EFFECTS OF MELATONIN: EVIDENCE BASED APPROACH

Hanaa H. Ahmed*, Samiha M. Abd El Dayem, Fatma M. Aly Foda, Abdel-Razik H. Farrag, Heba Abd El Raouf M

ABSTRACT

Depression is defined as mood disorder that is characterized by change in mood, lack of confidence and lack of interest in surroundings. The present study was planned to investigate the antidepressant activity of melatonin in the experimental model in attempt to clarify its mood of action. This study was conducted on 40 adult male albino rats assigned into 4 groups; Gp.(1) negative control group, Gp.(2) reserpinized group (positive control group) received reserpine in a dose of 0.1 mg/kg b.wt., Gp.(3) reserpinized group treated with low dose of melatonin(5 mg/kg b.wt.) and Gp.(4) reserpinized group treated with high dose of melatonin(10 mg/kg b.wt.) The behaviour test for all animals was done using forced swimming test (FST). Brain neurotransmitters (serotonin and dopamine) contents, the value of brain proinflammatory cytokines (IL-1β, IL-6 and TNF-α), the content of brain derived neutrophic factor (BDNF) and the level of the antiapoptic mediator (Bcl-2) as well as survivin expression in the brain tissue were carried out. In comparison with the negative control group, the reserpinized group recorded significant increase in the immobility time in the FST in concomitant with significant decrease in brain serotonin and dopamine contents and significant increase in the brain content of IL-1β, IL-6 and TNF-α . Moreover, significant decrease in brain BDNF and Bcl-2 contents were detected in the reserpinized group compared with the negative control group. Immunohistochemical examination of brain tissue using antibody against survivin showed weak positive reaction indicating low expression level of survivin in the brain of rats in the reserpinized group with respect to the negative control group. On the other hand, treatment of the reserpinized groups with either low or high dose of melatonin resulted in remarkable improvement in the behavioural, biochemical and immunohistocchemical parameters in a dose dependent manner. In conclusion, the present work provides a clear evidence for the antidepressant potential of melatonin through activation of serotoninergic and dopaminergic system, inhibition of proinflammatory cytokines, promotion of neurotrophic factor and upregulation of antiapoptic markers in the brain.

Keywords: Depression, Melatonin, Behaviour, neurotransmitters, Inflammation, Apoptosis.