Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
Clin Psychopharmacol Neurosci. 2014 Apr;12(1):31-6. doi: 10.9758/cpn.2014.12.1.31. Epub 2014 Apr 24.
Accumulating evidence suggests that inflammation plays a role in the pathophysiology of major depression. The adenosine triphosphate (ATP)-sensitive P2X7 receptor (P2X7R) plays a crucial role in microglial activation caused by inflammation. The dye brilliant blue G (BBG) is a P2X7R antagonist. This study examined whether BBG shows antidepressant effects in an inflammation-induced model of depression.
We examined the effects of BBG (12.5, 25, or 50 mg/kg) on serum tumor necrosis factor-α (TNF-α) levels after administering the bacterial endotoxin lipopolysaccharide (LPS; 0.5 mg/kg) and the effects of BBG (50 mg/kg) on depression-like behavior in the tail-suspension test (TST) and forced swimming test (FST).
Pretreatment with BBG (12.5, 25, or 50 mg/kg) significantly blocked the increase in serum TNF-α levels after a single dose of LPS (0.5 mg/kg). Furthermore, BBG (50 mg/kg) significantly attenuated the increase in immobility time in the TST and FST after LPS (0.5 mg/kg) administration.
The results suggest that BBG has anti-inflammatory and antidepressant effects in mice after LPS administration. Therefore, P2X7R antagonists are potential therapeutic drugs for inflammation-related major depression.
越来越多的证据表明,炎症在重度抑郁症的病理生理学中起作用。三磷酸腺苷(ATP)敏感的 P2X7 受体(P2X7R)在炎症引起的小胶质细胞激活中起关键作用。染料亮蓝 G(BBG)是一种 P2X7R 拮抗剂。本研究探讨了 BBG 在炎症诱导的抑郁症模型中是否具有抗抑郁作用。
我们观察了 BBG(12.5、25 或 50mg/kg)在给予细菌内毒素脂多糖(LPS;0.5mg/kg)后对血清肿瘤坏死因子-α(TNF-α)水平的影响,以及 BBG(50mg/kg)对尾悬试验(TST)和强迫游泳试验(FST)中抑郁样行为的影响。
BBG(12.5、25 或 50mg/kg)预处理可显著阻断单次 LPS(0.5mg/kg)给药后血清 TNF-α水平的升高。此外,BBG(50mg/kg)可显著减轻 LPS(0.5mg/kg)给药后 TST 和 FST 中不动时间的增加。
结果表明,BBG 在 LPS 给药后对小鼠具有抗炎和抗抑郁作用。因此,P2X7R 拮抗剂可能是治疗与炎症相关的重度抑郁症的潜在药物。