Grup de Recerca en Neurobiologia del Comportament-GReNeC, Departamento de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr. Aiguader 88, 08003 Barcelona, Spain.
Psychopharmacology (Berl). 2013 Mar;226(2):433-44. doi: 10.1007/s00213-012-2918-3. Epub 2012 Nov 29.
Previous research suggests that chronic daily caffeine administration protects against brain injury in different animal models of neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases, ischemic and traumatic brain injury, and allergic encephalitis. However, little is known about the effects of chronic caffeine administration on 3,4-methylenedioxymethamphetamine (MDMA)-induced neuroinflammation.
The present study examines whether chronic caffeine (10, 20, or 30 mg/kg, i.p, for 21 consecutive days) protects against MDMA-induced astrocytic and microglial activation in mice striatum, impairing its neuroinflammatory effects. Additionally, locomotor activity, sensoriomotor reflexes, body temperature, and anxiety were evaluated after caffeine injection on days 0 (basal), 7, 14, and 21 of the chronic treatment in order to assess possible behavioral alterations due to caffeine administration.
On day 22, mice pretreated with caffeine or saline received a neurotoxic regimen of MDMA (3 × 20 mg/kg, i.p., 2-h interval) or saline, and changes in body temperature were evaluated. Forty-eight hours after last MDMA or saline injection (day 24), the aforementioned behavioral parameters were investigated and microglia and astroglia activation to MDMA treatment was examined in the mouse striatum.
Caffeine (10 mg/kg) chronically administered completely prevented MDMA-induced glial activation without inducing physiological or behavioral alterations in any of the assays performed.
Chronic caffeine consumption at low doses exerts anti-inflammatory effects and prevents MDMA-induced neuroinflammation.
先前的研究表明，慢性每日咖啡因给药可预防不同神经退行性疾病动物模型中的脑损伤，如帕金森病和阿尔茨海默病、缺血性和创伤性脑损伤以及过敏性脑炎。然而，对于慢性咖啡因给药对 3,4-亚甲二氧基甲基苯丙胺（MDMA）诱导的神经炎症的影响知之甚少。
本研究旨在探讨慢性咖啡因（10、20 或 30mg/kg，腹腔注射，连续 21 天）是否可以预防 MDMA 诱导的小鼠纹状体星形胶质细胞和小胶质细胞激活，从而减轻其神经炎症作用。此外，在慢性治疗的第 0（基础）、7、14 和 21 天注射咖啡因后，评估运动活动、感觉运动反射、体温和焦虑，以评估由于咖啡因给药可能导致的行为改变。
在第 22 天，用咖啡因或生理盐水预处理的小鼠接受 MDMA（3×20mg/kg，腹腔注射，间隔 2 小时）或生理盐水的神经毒性方案，评估体温变化。在最后一次 MDMA 或生理盐水注射后 48 小时（第 24 天），研究了上述行为参数，并检查了小鼠纹状体中 MDMA 治疗后的小胶质细胞和星形胶质细胞激活情况。
慢性给予咖啡因（10mg/kg）可完全预防 MDMA 诱导的神经胶质细胞激活，而在任何进行的检测中均未引起生理或行为改变。
低剂量慢性咖啡因摄入具有抗炎作用，并可预防 MDMA 诱导的神经炎症。
