Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, USA.
Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, USA; Department of Psychiatry, The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, USA.
Pharmacol Biochem Behav. 2018 May;168:33-42. doi: 10.1016/j.pbb.2018.03.007. Epub 2018 Mar 20.
Neuroimmune cytokines are increased with alcohol withdrawal and may mediate clinical responses associated with alcoholism. Because minocycline regulates the level of cytokines, it has been suggested as a therapeutic for disorders associated with alcohol. Male Wistar rats were exposed to chronic intermittent alcohol (CIA) comprising three 5-day cycles of ethanol liquid diet separated by 2 days of withdrawal. Rats were tested on social interaction, a measure of anxiety-like behavior, followed immediately by collection of amygdala tissue to measure CCL2 and TNFα or collection of the blood to measure corticosterone (CORT). One group received a single minocycline injection 3 h into the final CIA withdrawal and was tested 2 h later. A second group received injections during each of the three withdrawals and was similarly tested during the final acute withdrawal. A third group received a single injection at 23 h into withdrawal (extended withdrawal) and was tested 6 h later. Results showed that CIA withdrawal increased anxiety-like behavior. A single injection of minocycline during the final acute withdrawal increased anxiety-like behavior in rats that consumed liquid diet with or without alcohol, but this effect disappeared with repeated injections of minocycline. Differences in alcohol intake, blood alcohol level, and plasma CORT levels did not explain results. Only repeated injections of minocycline decreased TNFα mRNA levels in rats that consumed liquid diet with or without alcohol. When a single injection of minocycline was given during extended withdrawal, it decreased CCL2 mRNA levels, but did not reverse the elevation of CCL2 protein. These results suggest that minocycline has actions in brain and on behavior, but minocycline does not significantly impact these actions in relation to alcohol withdrawal.
神经免疫细胞因子在酒精戒断时增加，并且可能介导与酒精中毒相关的临床反应。由于米诺环素可调节细胞因子的水平，因此它被提议作为与酒精相关的疾病的治疗方法。雄性 Wistar 大鼠暴露于慢性间歇性酒精（CIA）中，该酒精由三个乙醇液体饮食周期组成，每个周期之间间隔两天的戒断期。在社交互动测试后，立即收集杏仁核组织以测量 CCL2 和 TNFα，或收集血液以测量皮质酮（CORT）。一组大鼠在最后一次 CIA 戒断的 3 小时内接受一次米诺环素注射，并在 2 小时后进行测试。第二组大鼠在三个戒断期中的每个期中接受注射，并在最后一次急性戒断期间进行类似的测试。第三组大鼠在戒断的 23 小时时接受单次注射（延长戒断），并在 6 小时后进行测试。结果表明，CIA 戒断增加了焦虑样行为。在最后一次急性戒断期间单次注射米诺环素会增加摄入含酒精或不含酒精的液体饮食的大鼠的焦虑样行为，但这种作用在重复注射米诺环素后消失。酒精摄入量，血液酒精水平和血浆 CORT 水平的差异不能解释结果。只有重复注射米诺环素可降低摄入含酒精或不含酒精的液体饮食的大鼠的 TNFα mRNA 水平。当在延长的戒断期间单次注射米诺环素时，它降低了 CCL2 mRNA 水平，但没有逆转 CCL2 蛋白的升高。这些结果表明，米诺环素在大脑和行为上均有作用，但米诺环素对酒精戒断相关的这些作用没有明显影响。
