Lal H, Prather P L, Rezazadeh S M
Department of Pharmacology, Texas College of Osteopathic Medicine, Forth Worth 76107.
Alcohol Clin Exp Res. 1993 Apr;17(2):411-7. doi: 10.1111/j.1530-0277.1993.tb00785.x.
A single dose of mianserin (a 5HT1C/5HT2 antagonist), administered 1 hr, 48 hr, or 7 days before testing, was evaluated for its efficacy in alleviating or preventing the occurrence of anxiogenic behaviors observed during ethanol withdrawal. Other behavioral experiments using selected drug interactions were conducted to examine whether the effect of mianserin was related to a long-term modification of 5-hydroxy-tryptamine (5HT) receptor function. Rats were fed a liquid diet containing 4.5% ethanol for 4 days. They were tested on the elevated plus-maze (EPM) 12 hr (acute withdrawal) and 5 days (protracted withdrawal) after the last ethanol dose. Ethanol withdrawal induced a pattern of "anxiogenic" behavior that consisted of reduced activity (total entries) and a reduced proportion of open arm activity. Mianserin, injected as a single dose given either 1 hr (0.16-5 mg/kg, ip) before testing or given (20 mg/kg, ip) on the morning of the 3rd day of ethanol administration, i.e., 48 hr and 7 days before testing, dose-dependently prevented or reversed the ethanol withdrawal induced reduction in open-arm activity. In contrast, the 5HT1C/5HT2 receptor agonist (+/- )-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOl) did not affect behaviors in the EPM in ethanol-naive rats, nor in those undergoing ethanol withdrawal. However, although there was a marked tolerance to DOl-induced body shakes (a measure of 5HT2 function) during withdrawal, DOl reversed the action of mianserin in the EPM. The 5HT1 receptor agonist, 5HT2 receptor antagonist 1-naphthyl-piperazine (1-NP) reduced open-arm activity in ethanol-naive rats and this action was enhanced during withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
在测试前1小时、48小时或7天给予单剂量的米安色林（一种5HT1C/5HT2拮抗剂），评估其在减轻或预防乙醇戒断期间出现的焦虑行为方面的功效。使用选定药物相互作用进行的其他行为实验，以检查米安色林的作用是否与5-羟色胺（5HT）受体功能的长期改变有关。大鼠喂食含4.5%乙醇的液体饮食4天。在最后一次给予乙醇后12小时（急性戒断）和5天（延长戒断），在高架十字迷宫（EPM）上对它们进行测试。乙醇戒断诱导出一种“焦虑”行为模式，包括活动减少（总进入次数）和开放臂活动比例降低。米安色林作为单剂量在测试前1小时（0.16 - 5毫克/千克，腹腔注射）给予，或在乙醇给药第3天上午（即测试前48小时和7天）给予（20毫克/千克，腹腔注射），剂量依赖性地预防或逆转了乙醇戒断诱导的开放臂活动减少。相比之下，5HT1C/5HT2受体激动剂（±）-1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷盐酸盐（DOI）对未接触乙醇的大鼠以及正在经历乙醇戒断的大鼠在EPM中的行为没有影响。然而，尽管在戒断期间对DOI诱导的身体抖动（一种5HT2功能的测量指标）有明显耐受性，但DOI逆转了米安色林在EPM中的作用。5HT1受体激动剂、5HT2受体拮抗剂1-萘基哌嗪（1-NP）降低了未接触乙醇大鼠的开放臂活动，并且在戒断期间这种作用增强。（摘要截短于250字）
