Rezazadeh S M, Prather P L, Lal H
Department of Pharmacology, Texas College of Osteopathic Medicine, Fort Worth 76107.
Alcohol. 1993 Jul-Aug;10(4):281-3. doi: 10.1016/0741-8329(93)90006-a.
Anxiogenic action of m-chlorophenylpiperazine (mCPP), a 5-HT1C receptor agonist, was studied in naive rats and in ethanol-tolerant rats following withdrawal from chronic ethanol administration. The purpose of this investigation was to determine whether a sensitization to mCPP develops during withdrawal from chronic ethanol. Male Long-Evans hooded rats were fed a liquid diet containing 4.5% ethanol or dextrin (as control) for four days. Twelve hours (acute withdrawal) or 4 days (protracted withdrawal) after the last dose of ethanol, rats were injected with saline or mCPP (0.08-5.0 mg/kg) and were tested in the elevated plus-maze 15 min postinjection. A reduction in percent open-arm activity, indicative of anxiogenic behavior, was observed in ethanol-treated rats injected with saline. Administration of mCPP further reduced the percent open-arm entries and time in ethanol-withdrawn rats. An eightfold reduction in maximum effective dose of mCPP was observed during acute ethanol withdrawal as compared to that in naive rats. During protracted ethanol withdrawal the maximum effective dose of mCPP was reduced by 75%. A shift of the mCPP dose-response curve to the left following withdrawal from chronic ethanol may indicate that 5-HT1C receptor sites are more sensitive to the activation by an agonist. This effect may be exploited in developing specific 5-HT1C receptor antagonists for the treatment of ethanol withdrawal symptoms.
研究了5-HT1C受体激动剂间氯苯哌嗪（mCPP）对未接触过乙醇的大鼠以及长期给予乙醇后戒断的乙醇耐受大鼠的致焦虑作用。本研究的目的是确定在慢性乙醇戒断过程中是否会对mCPP产生敏感性。将雄性Long-Evans有帽大鼠用含4.5%乙醇或糊精（作为对照）的液体饲料喂养4天。在最后一剂乙醇后12小时（急性戒断）或4天（迁延性戒断），给大鼠注射生理盐水或mCPP（0.08 - 5.0毫克/千克），并在注射后15分钟在高架十字迷宫中进行测试。在注射生理盐水的乙醇处理大鼠中观察到开放臂活动百分比降低，这表明有致焦虑行为。给予mCPP进一步降低了乙醇戒断大鼠的开放臂进入百分比和停留时间。与未接触过乙醇的大鼠相比，在急性乙醇戒断期间观察到mCPP的最大有效剂量降低了八倍。在迁延性乙醇戒断期间，mCPP的最大有效剂量降低了75%。慢性乙醇戒断后mCPP剂量 - 反应曲线向左移动可能表明5-HT1C受体位点对激动剂的激活更敏感。这种效应可用于开发用于治疗乙醇戒断症状的特异性5-HT1C受体拮抗剂。
