Kelley B M, Bandy A L, Middaugh L D
Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston 29425-0742, USA.
Alcohol Clin Exp Res. 1997 Dec;21(9):1661-6.
The reinforcing effects of intravenous (I.V.) ethanol were examined in C57BL/6J (C57) mice with a conditioned-place-preference (CPP) paradigm. Before CPP testing, adult mice underwent jugular catheterization. On the following day, subjects were acclimated to a two-compartment CPP chamber. A 15-min nondrug pretest was conducted to determine compartment preference. For the treatment group, I.V. ethanol [30% (v/v), 3.4 microl/min, 25 min] was paired with the nonpreferred compartment, whereas I.V. saline was paired with the preferred compartment. The control group received I.V. saline in both compartments. Two conditioning sessions were conducted per day (0900 and 1500), and the order of the infusions was counterbalanced across subjects. The drug-free posttest was identical to the pretest, except that it occurred on the day after the final drug/compartment pairing. The entire procedure required 6 days. After just two pairings with ethanol, with a cumulative ethanol dose of only 0.82 g/kg/day, significant CPP was noted in the treatment group, whereas no change in compartment preference was noted for the control group. A separate group of C57 mice were trained to discriminate intraperitoneal ethanol (1.5 g/kg) from saline using a two-lever drug discrimination paradigm. After training was complete, these mice also underwent jugular catheterization. Substitution testing was conducted with I.V. ethanol [30% (v/v), 6.4 microl/min, 12 min] and saline. The results indicate that the subjective effects of ethanol did not differ according to the route of administration. Together, these experiments provide evidence that ethanol is rewarding for C57 mice, as indexed by ethanol CPP, and that the subjective effects of intravenously and intraperitoneally administered ethanol are similar.
采用条件性位置偏爱（CPP）范式，在C57BL/6J（C57）小鼠中研究静脉注射（I.V.）乙醇的强化作用。在进行CPP测试前，成年小鼠接受颈静脉插管。次日，将实验对象置于两室CPP箱中使其适应环境。进行15分钟的非药物预测试以确定对箱室的偏爱。对于治疗组，静脉注射乙醇[30%（v/v），3.4微升/分钟，25分钟]与非偏爱箱室配对，而静脉注射生理盐水与偏爱箱室配对。对照组在两个箱室中均接受静脉注射生理盐水。每天进行两次条件训练（上午9点和下午3点），输注顺序在各实验对象间进行平衡处理。无药物后测试与预测试相同，只是在最后一次药物/箱室配对后的次日进行。整个过程需要6天。仅与乙醇配对两次后，乙醇累积剂量仅为0.82克/千克/天，治疗组即出现显著的CPP，而对照组对箱室的偏爱无变化。另一组C57小鼠采用双杠杆药物辨别范式训练，以辨别腹腔注射乙醇（1.5克/千克）和生理盐水。训练完成后，这些小鼠也接受颈静脉插管。用静脉注射乙醇[30%（v/v），6.4微升/分钟，12分钟]和生理盐水进行替代测试。结果表明，乙醇的主观效应不因给药途径而异。总之，这些实验提供了证据，表明以乙醇CPP为指标，乙醇对C57小鼠具有奖赏作用，且静脉注射和腹腔注射乙醇的主观效应相似。
