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Objective: Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are potent interests due to disorganization of internal rhythms, which might have role in the pathophysiology of depression. The present study was designed to assess the effects of antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis in the stress induced depression model of rat brain.
Methods: Thirty-six Sprague Dawley male rats 220 to 250 g were used for study. Experimental stress was generated by light exposure for 1 hour twice a day for 1 week. After 1-week exposition of light, AG treatment was initiated at a dose of 10 mg/kg and 40 mg/kg concomitant to light exposure in stress-induced groups for a subsequent period of15 days. After the animals are scarified, tissue sections were obtained and stained immunohistochemically with anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum BDNF concentrations were measured biochemically by BDNF Elisa kit.
Results: Immunohistochemical analysis revealed that BrdU-positive cells counts were decreased in the hippocampus of stress-induced rats compared with control group. In addition, the treatment with low and high dose AG increased the BrdU-positive cell counts in the experimental stress exposed groups. In the pro-apoptotic caspase-3 analysis, there were more positive cells in the stress-exposed group compared with other groups. In addition, AG treatment decreased the caspase-3 immune positive cell counts. In anti-apoptotic Bcl-2 staining, although there were fewer immunologically positive cell counts in the stress group. Biochemical analysis revealed the high concentration of BDNF in the serum of stress-exposed group, but the concentration of BDNF was decreased in the AG treated groups. There were statistically significant difference between no-stress groups treated with AG and control group (p<0.05).
Conclusion: The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increase the hippocampal neurogenesis. Moreover, these results amplify the possible relationship between depression and adult neurogenesis, which must be further study.