Purinergic 2X7 receptor (P2X7R) activation has recently been considered to be involved in depression at least partially by triggering microglial activation. The aim of the present study was to examine whether the chronic administration of brilliant blue G (BBG), a highly selective P2X7R antagonist, has antidepressant-like effects and microglial (Iba-1) immunoreactivity in chronic unpredictable mild stress (CUMS) model in rats.

Male Wistar Albino rats (290–360 g) were divided into groups such as control (saline), CUMS, CUMS + Imipramine (20 mg/kg; i.p.), CUMS + BBG25 (25 mg/kg; i.p.), CUMS + BBG50 (50 mg/kg; i.p.) groups (n = 10–12 in each). In CUMS model, various stressors were applied for 40 days. On day 20, the treatment of BBG was started for 20 days. At the end, sucrose preference and forced swimming tests were performed. Then brains were removed with paraformaldehyde perfusion for Iba-1 immunohistochemical analysis in hippocampus. One-way analysis of variance and Tukey's test were used for statistical analysis.

The time of immobility in forced swim test was significantly reduced while sucrose preference was increased in Imipramine and CUMS + BBG50 groups compared to control and CUMS groups, respectively. In immunohistochemical experiments, Iba-1 was overexpressed in CUMS group and BBG significantly reduced the overexpression of Iba-1.

Our results suggest that chronic administration of BBG has an antidepressant-like activity supporting the notion of P2X7 receptors involvement in depression by modulating microglial activation.

This research was supported by grant from Marmara University, Scientific Research Projects – SAG-C-YLP-110915-0416 and SAG-E-120613-0233.

The authors have not supplied their declaration of competing interest.