Antidepressant-like Effects Induced by Chronic Blockade of the Purinergic 2X7 Receptor through Inhibition of Non-like Receptor Protein 1 Inflammasome in Chronic Unpredictable Mild Stress Model of Depression in Rats.

摘要: Objective Purinergic 2X7 receptor (P2X7R) activation is known to be involved in pathogenesis of depression. Our aims were investigate P2X7R-activated inflammasome pathways parallel with induction depression and test the antidepressant-like effects selective P2X7R antagonist Brilliant Blue G (BBG) a rat model chronic unpredictable mild stress (CUMS). Methods Male Wistar albino rats divided into control, CUMS, CUMS＋BBG25 (25 mg/kg/day) CUMS＋BBG50 (50 groups (n=10 for each group). Various stressors applied 6 weeks establish CUMS daily BBG treatment was started at end 3rd week. Sucrose preference forced swim (FST) performed assess effects. Brain samples obtained real-time polymerase chain reaction immunohistochemistry analysis. Results In FST, duration immobility reduced group. Also, significantly enhanced sucrose preference. While NLRP3 gene expression levels unchanged exposed protocol, other pathway factors NLRP1, caspase-1, ASC, NF-κB, IL-1β, IL-6 increased. these factors. Likewise, Iba-1 GFAP immunoreactivities by protocol this action reversed treatment. Conclusion Chronic administration results activity dose dependent manner. Molecular histological show that might least partially related suppression inflammasome-related neuroinflammatory responses suggest involvement NLRP1