Depressive and anxious behaviors are the most common psychiatric symptoms of epilepsy, and may aggravate the epileptic condition and affect the patient's quality of life. Accumulating data obtained from both experimental animal models and patients have convincingly shown a critical role of P2X7 receptor (P2X7R) during depression and anxiety. Our study showed for the first time that the P2X7R is involved in promoting depression- and anxiety-like behaviors in lithium pilocarpine-induced epileptic rats. More importantly, direct anti-depressive and anti-anxiety effects were produced by the P2X7R antagonist Brilliant Blue G (BBG) is in this study, and the effect was similar to that of the classic anti-depressant and anti-anxiety drug fluoxetine. We also found that BBG did not affect the development of spontaneous recurrent seizures (SRS) and had a neuroprotective effect via inhibition of microglial activation after status epilepticus (SE). Thus, our data provide evidence that the P2X7R in activated microglia promotes depression- and anxiety-like behaviors in lithium-pilocarpine induced epileptic rats. Since previous studies have indicated that some anti-depression and anti-anxiety drugs may exacerbate seizures, our data support that the P2X7R is a promising therapeutic target for epilepsy associated with depression and anxiety.

抑郁和焦虑行为是癫痫最常见的精神症状，可能会加重癫痫的病情，影响患者的生活质量。从实验动物模型和患者中获得的累积数据已经令人信服地显示了 P2X7 受体 (P2X7R) 在抑郁和焦虑期间的关键作用。我们的研究首次表明 P2X7R 参与促进毛果芸香碱锂诱导的癫痫大鼠的抑郁和焦虑样行为。更重要的是，本研究中的P2X7R拮抗剂Brilliant Blue G（BBG）产生了直接的抗抑郁和抗焦虑作用，其作用与经典的抗抑郁和抗焦虑药物氟西汀相似。我们还发现 BBG 不影响自发性复发性癫痫 (SRS) 的发展，并且通过抑制癫痫持续状态 (SE) 后小胶质细胞的激活具有神经保护作用。因此，我们的数据提供的证据表明，活化的小胶质细胞中的 P2X7R 促进了锂-毛果芸香碱诱导的癫痫大鼠的抑郁和焦虑样行为。由于之前的研究表明一些抗抑郁和抗焦虑药物可能会加剧癫痫发作，我们的数据支持 P2X7R 是与抑郁和焦虑相关的癫痫的有希望的治疗靶点。