Does Agomelatine Have Antidepressant Action in Juvenile Rats? (1144.4)

The purpose of this project is to investigate the effects of agomelatine on hippocampal neurogenesis and behavior in juvenile rats, which may lead to testing agomelatine for treating juvenile depression. Postnatal day 21 (PND21) juvenile Sprague‐Dawley rats were divided into 2 subgroups: 1) neurogenesis, and 2) behavioral. Each subgroup was further divided into experimental and control groups and injected intraperitoneally (IP) with agomelatine (10 mg kg¯¹) in 1% hydroxyethyl cellulose or vehicle respectively. The neurogenesis subgroup was injected once daily for 14 days. The behavioral subgroup was injected for 3 days, the first 2 days according to a porsolt forced swim test protocol, and once on the third day. The neurogenesis subgroup was also injected IP with BrdU three times a day for two days at the end, mitogenic, or the beginning, cell survival, of the 14 day injection period. After BrdU administration, the rats were sacrificed, and brain tissues fixed. The fixed brains were sectioned and analyzed using immunohistochemistry to detect BrdU and NeuN to assess differences in hippocampal mitogenesis and neurogenesis. The behavioral subgroup was subjected to a porsolt forced swim test to predict antidepressant activity, an open field test to detect locomotor differences, and an elevated plus maze to detect anxiety differences. Preliminary results show behavioral and structural trends that may be characteristic of an antidepressant effect. The results of the forced swim test showed that agomelatine decreased immobility time, which predicts agomelatine may be an antidepressant. There was not a significant difference between groups in the open field and elevated plus maze tests. The preliminary immunohistochemistry analysis of mitogenesis demonstrated an increased number of hippocampal cells in the subgranular zone (SGZ) and hilus. The analysis of neurogenesis with 10 mg kg¯¹ of agomelatine is underway. Agomelatine may act as an antidepressant drug in juvenile rats.