Lal H, Prather P L, Rezazadeh S M
Department of Pharmacology, Texas College of Osteopathic Medicine, Ft. Worth 76107.
Alcohol. 1991 Nov-Dec;8(6):467-71. doi: 10.1016/s0741-8329(91)90153-n.
This study investigated the effectiveness of buspirone in reversing the anxiogenic behaviors occurring during ethanol withdrawal as measured in the elevated plus-maze. In response to anxiogenic drugs, rats spend less time in and make fewer entries onto the open arms of an elevated plus-maze, whereas anxiolytic drugs produce opposite effects. In this study, rats were fed a liquid diet containing 4.5% ethanol for 7 days. Twelve h (acute withdrawal) and 7 days (protracted withdrawal) following cessation of the ethanol diet, rats were tested on the elevated plus-maze. During these withdrawal periods, the percent open-arm entries and time spent on the open arms were significantly reduced relative to animals fed an ethanol-free diet, suggestive of anxiogenic-like symptoms. Buspirone (0.32-1.25 mg/kg) dose dependently reversed the withdrawal-induced decreases in open-arm activity. The anxiolytic-like activity of buspirone observed during ethanol withdrawal may be due to a reduction in serotonergic neurotransmission through activation of presynaptic 5-HT1A autoreceptors. The results obtained in this study suggest that pharmacotherapy with selective 5-HT1A agonists may be beneficial in alleviation of anxiety during ethanol withdrawal.
本研究调查了丁螺环酮逆转乙醇戒断期间在高架十字迷宫中所测到的致焦虑行为的有效性。对致焦虑药物的反应是，大鼠在高架十字迷宫开放臂上停留的时间减少且进入开放臂的次数减少，而抗焦虑药物则产生相反的效果。在本研究中，给大鼠喂食含4.5%乙醇的液体饲料7天。在停止乙醇饲料喂养后的12小时（急性戒断）和7天（迁延性戒断），对大鼠进行高架十字迷宫测试。在这些戒断期间，与喂食无乙醇饲料的动物相比，开放臂进入百分比和在开放臂上花费的时间显著减少，提示有致焦虑样症状。丁螺环酮（0.32 - 1.25毫克/千克）剂量依赖性地逆转了戒断诱导的开放臂活动减少。在乙醇戒断期间观察到的丁螺环酮的抗焦虑样活性可能是由于通过激活突触前5-HT1A自身受体减少了血清素能神经传递。本研究获得的结果表明，用选择性5-HT1A激动剂进行药物治疗可能有助于缓解乙醇戒断期间的焦虑。
