Sullivan J T
Johns Hopkins University School of Medicine, Department of Medicine, Francis Scott Key Medical Center, Baltimore MD 21224.
Life Sci. 1993;52(15):1295-300.
This study investigated the effects of verapamil on the acquisition of tolerance to the ataxic effects of ethanol. Four groups of rats (n = 20/group) were randomly assigned to oral treatment regimes. One group received chronic ethanol treatment (starting at 5 gm/kg/day and increasing by 1 gm/kg at weekly intervals to an eventual dose of 9 gm/kg/day). A second group received the same dose of chronic ethanol together with verapamil (10 mg/kg twice daily). A third group received the same dose of chronic verapamil while the fourth group received chronic placebo treatment. Every fourth day all rats received at least a 2 gm/kg ip test dose of ethanol. Following this, change in motor coordination was measured on an accelerating Rota-Rod treadmill. After six weeks the chronic ethanol group developed tolerance to the test dose of ethanol, while the ethanol and verapamil group did not. Blood ethanol concentrations were not different between the groups. The chronic verapamil and placebo groups developed sensitization to the effects of ethanol but were not different from each other. Chronic treatment with verapamil appeared to delay the acquisition of chronic tolerance to ethanol.
本研究调查了维拉帕米对乙醇所致共济失调耐受性获得的影响。将四组大鼠（每组n = 20）随机分配至口服治疗方案。一组接受慢性乙醇治疗（起始剂量为5克/千克/天，每周间隔增加1克/千克，最终剂量为9克/千克/天）。第二组接受相同剂量的慢性乙醇并联合维拉帕米（每日两次，每次10毫克/千克）。第三组接受相同剂量的慢性维拉帕米，而第四组接受慢性安慰剂治疗。每四天所有大鼠至少接受一次2克/千克腹腔注射乙醇测试剂量。在此之后，在加速转动杆跑步机上测量运动协调性变化。六周后，慢性乙醇组对乙醇测试剂量产生了耐受性，而乙醇和维拉帕米组则未产生。各组之间的血液乙醇浓度无差异。慢性维拉帕米组和安慰剂组对乙醇的作用产生了敏化，但彼此之间无差异。维拉帕米的慢性治疗似乎延迟了对乙醇慢性耐受性的获得。
