Prather P L, Rezazadeh S M, Lal H
Department of Pharmacology, Texas College of Osteopathic Medicine, Fort Worth 76107.
Psychopharmacol Bull. 1991;27(3):285-9.
The present investigation was a pilot study to determine whether a single dose of mianserin, which produces long-term down-regulation of serotonin1C (5-HT1c) and 5-HT2 receptors, would prevent anxiogenic behaviors occurring during ethanol withdrawal as evaluated in the elevated plus maze. Male Long-Evans hooded rats were fed a liquid diet containing 4.5 percent ethanol for 4 days. Mianserin (20 mg/kg, i.p.) was injected on the morning of the third day of ethanol administration, or 48 hrs and 7 days prior to testing. When animals were tested either 12 hrs (acute withdrawal) or 5 days (protracted withdrawal) after the last dose of ethanol, anxiogenic behaviors were observed as a significant reduction in both percentage of open-arm entries and time spent on the open arms. In contrast, these anxiogenic behaviors were prevented by pre-injection with mianserin 48 hrs or 7 days prior to testing. Attenuation of this important symptom of ethanol withdrawal is of particular importance because, in addition to the nonaddicting properties of mianserin relative to current anxiolytics, the beneficial effects appear to be long lasting and can be achieved with a single dose.
本研究是一项初步研究，旨在确定单剂量米安色林（可导致5-羟色胺1C（5-HT1c）和5-HT2受体长期下调）是否能预防乙醇戒断期间在高架十字迷宫实验中所评估的焦虑行为。雄性Long-Evans有帽大鼠喂食含4.5%乙醇的液体饮食4天。在给予乙醇的第三天上午，或在测试前48小时和7天注射米安色林（20毫克/千克，腹腔注射）。当动物在最后一剂乙醇后12小时（急性戒断）或5天（迁延性戒断）接受测试时，观察到焦虑行为表现为进入开放臂的百分比和在开放臂上花费的时间均显著减少。相比之下，在测试前48小时或7天预先注射米安色林可预防这些焦虑行为。减轻乙醇戒断的这一重要症状尤为重要，因为除了米安色林相对于目前抗焦虑药的非成瘾特性外，其有益效果似乎持久，且单剂量即可实现。
