Agomelatine-induced modulation of brain-derived neurotrophic factor (BDNF) in the rat hippocampus

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that serves as a survival factor for neurons. Agomelatine is a novel antidepressant as well as a potent agonist of melatonin (MT), MT1 and MT2 receptor types and an antagonist of the serotonin (5HT), 5-HT_2C receptor. The study herein established whether treatment with agomelatine alters hippocampal BDNF protein expression under chronic unpredictable mild stress (CUMS) condition. Twenty-one day treatment with agomelatine, fluoxetine or vehicle was assessed in 52 Sprague-Dawley rats undergoing CUMS. Ten naïve control rats were also evaluated after 21 days. The behavioral effects of treatments were studied using the open field test (OFT) on day 0, 7 and 21 and sucrose preference test on day 21. Hippocampal BDNF protein expression was measured using immunohistochemistry. The effect of the interventions on hippocampal neurons was histologically examined after H&E staining. Agomelatine mitigated the reduction in rearing behavior by CUMS in the OFT on day 7 as well as sucrose preference on day 21. The mean optical density value of BDNF was significantly higher in the CUMS + agomelatine group than the CUMS and CUMS + fluoxetine groups. The CUMS + agomelatine group had a significantly higher number of BDNF positive cells compared to naïve controls and CUMS group. Histology showed that hippocampal neurons in the CUMS + agomelatine and CUMS + fluoxetine groups were intact and few of them demonstrated karyopyknosis. Agomelatine-a novel antidepressant, but not fluoxetine, increased hippocampal BDNF level and of BDNF positive neurons in rats subject to CUMS.