South Plains Alcohol and Addiction Research Center, Department of Pharmacology and Neurosciences, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Brain Behav Immun. 2011 Jun;25 Suppl 1(Suppl 1):S165-9. doi: 10.1016/j.bbi.2011.03.002. Epub 2011 Mar 21.
Alcoholism is a disease characterized by continued alcohol consumption despite recurring negative consequences. Thus, medications that reduce the drive to consume alcohol can be beneficial in treating alcoholism. The neurobiological systems that regulate alcohol consumption are complex and not fully understood. Currently, medications are available to treat alcoholism that act either by causing accumulation of a toxic metabolite of ethanol, or by targeting specific transmitter receptors. The purpose of our study was to investigate a new potential therapeutic pathway, neuroimmune interactions, for effects on ethanol consumption. We hypothesized that neuroimmune activity of brain glia may have a role in drinking. We utilized minocycline, a second generation tetracycline antibiotic that has immune modulatory actions, to test our hypothesis because it is known to suppress microglia, and to a lesser extent astroglia, activity following many types of insults to the brain. Treatment with 50mg/kg minocycline significantly reduced ethanol intake in male and female C57Bl/6J mice using a free choice voluntary drinking model. Saline injections did not alter ethanol intake. Minocycline had little effect on water intake or body weight change. The underlying mechanism whereby minocycline reduced ethanol intake requires further study. The results suggest that drugs that alter neuroimmune pathways may represent a new approach to developing additional therapies to treat alcoholism.
酒精中毒是一种疾病,其特征是尽管反复出现负面后果,但仍持续饮酒。因此,减少饮酒欲望的药物在治疗酒精中毒方面可能是有益的。调节饮酒的神经生物学系统很复杂,尚未完全了解。目前,有一些药物可用于治疗酒精中毒,这些药物的作用方式要么是导致乙醇的有毒代谢物积累,要么是针对特定的递质受体。我们研究的目的是研究神经免疫相互作用的新的潜在治疗途径对乙醇消耗的影响。我们假设脑胶质细胞的神经免疫活性可能在饮酒中起作用。我们利用米诺环素(一种具有免疫调节作用的第二代四环素抗生素)来检验我们的假设,因为它已知可以抑制脑损伤后的小胶质细胞,并且在较小程度上抑制星形胶质细胞的活性。使用自由选择自愿饮酒模型,用 50mg/kg 米诺环素治疗可显著减少雄性和雌性 C57Bl/6J 小鼠的乙醇摄入量。生理盐水注射不会改变乙醇摄入量。米诺环素对水摄入量或体重变化影响不大。减少乙醇摄入的潜在机制需要进一步研究。结果表明,改变神经免疫途径的药物可能代表开发治疗酒精中毒的新疗法的新方法。