Graduate School of Biomedical Science and Engineering, University of Maine, Orono, Maine.
Department of Psychology, University of Maine, Orono, Maine.
Alcohol Clin Exp Res. 2019 Jul;43(7):1478-1485. doi: 10.1111/acer.14074. Epub 2019 May 21.
While the acute alcohol withdrawal syndrome has been well characterized both in human clinical studies and in experimental animals, much less is known regarding long-term affective disturbances that can sometimes persist during protracted abstinence. Nevertheless, since relapse often occurs long after acute detoxification and may be predicted by persistent affective disruption, a better understanding of the long-term behavioral consequences of prior alcohol dependence may lead to improved strategies for relapse prevention.
Male and female Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant mice from the second selection replicate (WSP-2, WSR-2) were exposed to a 10-day chronic-intermittent ethanol vapor protocol (CIE) or plain air and then tested repeatedly on the sucrose preference test (SPT), marble burying test (MBT), and the light-dark box test (LDT) over 7 weeks of (forced) abstinence.
While WSP and WSR mice differed significantly on tests of anxiety-like behavior (LDT, MBT), we found little evidence for long-term affective disruption following CIE in either line. The major exception was in the LDT, in that WSP but not WSR mice displayed longer latencies to enter the light compartment following CIE relative to air-controls.
Selective breeding for acute withdrawal severity has resulted in differences in anxiety-like behavior between WSP and WSR mice. In contrast, however, genes contributing to the severity of acute withdrawal convulsions appear to have little overlap with those predisposing to affective disruption during long-term abstinence.
虽然急性酒精戒断综合征在人类临床研究和实验动物中已经得到了很好的描述，但对于长期的情感障碍知之甚少，这些障碍有时会在长期戒断期间持续存在。然而，由于复发通常发生在急性解毒后很久，并且可能会被持续的情感障碍所预测，因此更好地了解先前酒精依赖的长期行为后果可能会导致改善预防复发的策略。
来自第二次选择复制（WSP-2、WSR-2）的雄性和雌性戒断性癫痫易发性和戒断性癫痫抗性小鼠暴露于 10 天的慢性间歇性乙醇蒸气方案（CIE）或普通空气中，然后在蔗糖偏好测试（SPT）、大理石掩埋测试（MBT）和明暗箱测试（LDT）上反复测试，在 7 周的（强制）戒断期间。
尽管 WSP 和 WSR 小鼠在焦虑样行为测试（LDT、MBT）上存在显著差异，但我们发现 CIE 在两条线中均未显示出长期的情感障碍。主要的例外是在 LDT 中，WSP 而不是 WSR 小鼠在 CIE 后进入亮区的潜伏期较长相对于空气对照。
急性戒断严重程度的选择性繁殖导致 WSP 和 WSR 小鼠之间出现焦虑样行为的差异。然而，相反，导致急性戒断抽搐严重程度的基因与导致长期戒断期间情感障碍的基因重叠很少。
