Acute blockade of P2X7 receptors by Brilliant Blue G does not result in antidepressant-like activity in mice

Objective: Purinergic 2X7 receptor activation has recently been considered to be possibly involved in depression by resulting in excessive glutamatergic neurotransmission and also increased release of proinşammatory cytokines through NLRP3 inşammasome pathway. In very recent studies, PPADS and iso-PPADS, non-selective P2R and P2XR antagonists respectively, are shown to have acute antidepressant-like effects and genetic deletion of P2X7R induces antidepressive-like state in mice. Therefore, the aim of the present study is to investigate whether the acute administration of Brilliant Blue G (BBG), a highly selective P2X7R antagonist, has antidepressant-like effects in forced swim (FST) and tail suspension tests (TST) in mice.

Methods: Balb-c mice (20-40 g) were divided into Control (saline), Imipramine (30 mg/kg), BBG (100 mg/kg), Imipramine +BBG (30 mg/kg+100 mg/kg) groups (n=10-14 in each). FST and TST were applied to distinct groups 30 min after i.p. drug administration for assessing the acute antidepressant-like effects of BBG. Mice subjected to FST or TST were allowed to swim for 6 min (temperature remained at 23-25 °C) or suspended by the tails for 5 min, respectively. The time of immobility was video recorded and scored by three different trained experimenters. One-way analysis of variance (ANOVA) was used for statistical analysis followed by Tukey’s test.

Results: The time of immobility was significantly reduced in Imipramine (30 mg/kg) groups compared to control (saline) groups (FST; p<0.001, TST; p<0.01). The time of immobility in BBG (100 mg/kg) groups were not statistically different when compared to control groups. When combined with Imipramine, the immobility time was reduced significantly compared to BBG alone (FST; p<0.001, TST; p<0.05) and control (TST; p<0.01).

Conclusions: Our present results from the both despair models suggest that acute administration of BBG did not result in antidepressant-like activity. Further, BBG does not enhance or reverse the antidepressant effect of imipramine that can be interpreted as not interacting with serotonergic neurotransmission. These results strongly support our notion that questioning P2X7 receptors involvement in depression requires activation of NLRP3 inşammasome by ATP-mediated danger stimulus such as stress in psychiatric manner. Therefore, future studies are needed to further investigate the role of P2X7 receptor activation in stress-mediated chronic pathologies as in depression.