Department of Neurosciences, University of Toledo College of Medicine, 3000 Arlington Avenue, Toledo, OH, 43614, USA.
Department of Pharmacology and Toxicology, Indiana University School of Medicine, 635 Barnhill Drive, MS A401, Indianapolis, IN, 46202, USA.
J Neuroimmune Pharmacol. 2018 Mar;13(1):53-63. doi: 10.1007/s11481-017-9764-3. Epub 2017 Aug 30.
A majority of methamphetamine (Meth) abusers also abuse alcohol but the neurochemical consequences of this co-abuse are unknown. Individually, alcohol and Meth cause inflammation and long-term alterations in dopamine and serotonin signaling within the brain. Experiments were conducted to identify if serial exposure to alcohol and Meth has neurochemical consequences that are greater than after either drug alone. Male Sprague Dawley rats voluntarily drank 10% ethanol (EtOH) every other day for 4 weeks and were then exposed to a binge injection regimen of Meth (10 mg/kg injected every 2 h, for a total of 4 injections). EtOH drinking and preference increased over the 4 weeks and caused inflammation evidenced by increases in serum and brain lipopolysaccharide (LPS) and brain cyclooxygenase-2 (COX-2) 24 h after the last day of drinking. Meth alone depleted dopamine and serotonin in the striatum, as well as serotonin in the prefrontal cortex when measured 1 week later. In contrast, EtOH drinking alone did not affect dopamine and serotonin content in the striatum and prefrontal cortex, but prior EtOH drinking followed by injections of Meth enhanced Meth-induced depletions of dopamine, serotonin, as well as dopamine and serotonin transporter immunoreactivities in a manner that was correlated with the degree of EtOH consumption. Cyclooxygenase inhibition by ketoprofen during EtOH drinking blocked the increases in LPS and COX-2 and the enhanced decreases in dopamine and serotonin produced by Meth. Therefore, prior EtOH drinking causes an increase in inflammatory mediators that mediate a synergistic interaction with Meth to cause an enhanced neurotoxicity.
大多数甲基苯丙胺（冰毒）滥用者也同时滥用酒精，但这种共滥用的神经化学后果尚不清楚。单独使用酒精和冰毒会导致大脑中多巴胺和血清素信号的炎症和长期改变。进行实验以确定连续暴露于酒精和冰毒是否会导致比单独使用任何一种药物更大的神经化学后果。雄性 Sprague Dawley 大鼠每隔一天自愿饮用 10%乙醇（EtOH）4 周，然后接受冰毒 binge 注射方案（每 2 小时注射 10mg/kg，总共 4 次注射）。EtOH 饮酒和偏好在 4 周内增加，并导致炎症，表现为最后一天饮酒后 24 小时血清和大脑脂多糖（LPS）以及大脑环氧化酶-2（COX-2）增加。单独的冰毒耗尽了纹状体中的多巴胺和血清素，以及前额叶皮层中的血清素，1 周后测量时也是如此。相比之下，单独饮酒 EtOH 不会影响纹状体和前额叶皮层中的多巴胺和血清素含量，但之前的 EtOH 饮酒后再注射冰毒会增强冰毒诱导的多巴胺、血清素以及多巴胺和血清素转运蛋白免疫反应性的耗竭，这种增强与 EtOH 消耗的程度相关。在 EtOH 饮酒期间用酮洛芬抑制环氧化酶会阻断 LPS 和 COX-2 的增加，以及冰毒引起的多巴胺和血清素的增强性减少。因此，先前的 EtOH 饮酒会导致炎症介质增加，这些介质与冰毒协同作用，导致神经毒性增强。
