Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, L470, 3181 SW Sam Jackson Park Road, Portland, OR, 97239-3098, USA.
Area de Psicobiología, Universitat Jaume I, 12071, Castellón, Spain.
Psychopharmacology (Berl). 2017 Sep;234(18):2747-2759. doi: 10.1007/s00213-017-4672-z. Epub 2017 Jun 26.
Previous studies found that naloxone (NLX) facilitated choice extinction of ethanol conditioned place preference (CPP) using long (60 min) test sessions, but there is little information on the variables determining this effect.
These studies examined repeated exposure to NLX during extinction of ethanol- or cocaine-induced CPP using both short and long tests.
DBA/2J mice were injected with NLX (0 or 10 mg/kg) before three 10- or 60-min choice extinction tests (experiment 1). All mice received a final 60-min test without NLX. Post-test NLX was given in experiment 2. Experiment 3 tested whether NLX would affect a forced extinction procedure. Experiment 4 tested its effect on extinction of cocaine-induced CPP.
Pre-test (but not post-test) injections of NLX-facilitated choice extinction of ethanol CPP at both test durations. Pre-test NLX also facilitated forced extinction. However, pre-test NLX had no effect on choice extinction of cocaine CPP.
Extinction test duration is not critical for engaging the opioid system during ethanol CPP extinction (experiment 1). Moreover, NLX's effect does not depend on CPP expression during extinction, just exposure to previously conditioned cues (experiment 3). The null effect of post-test NLX eliminates a memory consolidation interpretation (experiment 2) and the failure to alter cocaine CPP extinction argues against alteration of general learning or memory processes (experiment 4). Overall, these data suggest that the endogenous opioid system mediates a conditioned motivational effect that normally maintains alcohol-induced seeking behavior, which may underlie the efficacy of opiate antagonists in the treatment of alcoholism.
先前的研究发现，纳洛酮（NLX）通过长（60 分钟）测试疗程促进乙醇条件位置偏好（CPP）的选择消退，但关于确定这种效果的变量的信息很少。
这些研究使用短程和长程测试检查了在乙醇或可卡因诱导的 CPP 消退过程中，NLX 在消退过程中的重复暴露。
DBA/2J 小鼠在三次 10 或 60 分钟选择消退测试（实验 1）之前接受 NLX（0 或 10mg/kg）注射。所有小鼠均接受无 NLX 的最后 60 分钟测试。实验 2 中给予测试后 NLX。实验 3 测试了 NLX 是否会影响强制消退程序。实验 4 测试了它对可卡因诱导的 CPP 消退的影响。
预测试（而不是测试后）注射 NLX 可促进乙醇 CPP 在两种测试持续时间下的选择消退。预测试 NLX 还促进了强制消退。然而，预测试 NLX 对可卡因 CPP 的消退没有影响。
在乙醇 CPP 消退期间，消退测试持续时间对于参与阿片系统并不关键（实验 1）。此外，NLX 的作用不依赖于消退过程中的 CPP 表达，而仅依赖于对先前条件刺激的暴露（实验 3）。测试后 NLX 的无效作用消除了记忆巩固的解释（实验 2），并且未能改变可卡因 CPP 的消退表明一般学习或记忆过程没有改变（实验 4）。总体而言，这些数据表明内源性阿片系统介导了一种调节动机的效应，该效应通常维持着酒精引起的寻求行为，这可能是阿片类拮抗剂在治疗酒精中毒中的疗效的基础。
