Department of Pharmaceutical Sciences, The University of Kentucky, Lexington, 40536-0082, USA.
Alcohol. 2010 Feb;44(1):89-98. doi: 10.1016/j.alcohol.2009.10.017.
Alcohol use during adolescence leads to increased risk of developing an alcohol use disorder (AUD) during adulthood. Converging evidence suggests that this period of enhanced vulnerability for developing an AUD may be due to the adolescent's unique sensitivity and response to alcohol. Adolescent rats have been shown to be less sensitive to alcohol intoxication and withdrawal susceptibility; however, age differences in ethanol pharmacokinetics may underlie these effects. Therefore, this study investigated alcohol intoxication behavior and withdrawal severity using a modified Majchrowicz model of alcohol dependence that has been shown to result in similar blood ethanol concentrations (BECs) despite age differences. Adolescent (postnatal day, PND, 35) and adult rats (PND 70+) received ethanol according to this 4-day binge paradigm and were observed for withdrawal behavior for 17h. As expected, adolescents showed decreased sensitivity to alcohol-induced CNS depression as evidenced by significantly lower intoxication scores. Thus, adolescents received significantly more ethanol each day (12.3+/-0.1g/kg/day) than adults (9.2+/-0.2g/kg/day). Despite greater ethanol dosing in adolescent rats, both adolescent and adult groups had comparable peak BECs (344.5+/-10.2 and 338.5+/-7.8mg/dL, respectively). Strikingly, withdrawal severity was similar quantitatively and qualitatively between adolescent and adult rats. Further, this is the first time that withdrawal behavior has been reported for adolescent rats using this model of alcohol dependence. A second experiment confirmed the similarity in BECs at various time points across the binge. These results demonstrate that after consideration of ethanol pharmacokinetics between adults and adolescents by using a model that produces similar BECs, withdrawal severity is nearly identical. This study, in combination with previous reports on ethanol withdrawal in adolescents and adults, suggests only a BEC-dependent effect of ethanol on withdrawal severity regardless of age.
青少年时期饮酒会增加成年后患酒精使用障碍（AUD）的风险。越来越多的证据表明，青少年在这段时间内对 AUD 的易感性增强可能是由于他们对酒精的独特敏感性和反应。研究表明，与成年大鼠相比，青春期大鼠对酒精中毒和戒断易感性的敏感性较低；然而，乙醇药代动力学的年龄差异可能是这些影响的基础。因此，本研究使用 Majchrowicz 酒精依赖模型，该模型已被证明在年龄差异的情况下会导致相似的血液乙醇浓度（BEC），从而研究了酒精中毒行为和戒断严重程度。该模型使用 4 天 binge 范式，给青春期（出生后第 35 天）和成年大鼠（出生后第 70 天以上）灌酒，并观察 17 小时的戒断行为。正如预期的那样，青少年对酒精引起的中枢神经系统抑制的敏感性降低，表现为醉酒评分显著降低。因此，青少年每天摄入的酒精量明显多于成年大鼠（12.3+/-0.1g/kg/day）（9.2+/-0.2g/kg/day）。尽管青春期大鼠给予的乙醇剂量较大，但两组的峰值 BEC 相似（分别为 344.5+/-10.2 和 338.5+/-7.8mg/dL）。引人注目的是，青春期和成年大鼠的戒断严重程度在数量和质量上相似。此外，这是首次使用这种酒精依赖模型报告青春期大鼠的戒断行为。第二项实验证实了 binge 期间不同时间点 BEC 的相似性。这些结果表明，在考虑了成年和青少年之间的乙醇药代动力学后，通过使用产生相似 BEC 的模型，戒断严重程度几乎相同。本研究结合之前关于青少年和成年乙醇戒断的报告表明，无论年龄如何，乙醇对戒断严重程度的影响仅取决于 BEC。
