Rezvani Amir H, Levin Edward D
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
Pharmacol Biochem Behav. 2002 Jul;72(4):865-72. doi: 10.1016/s0091-3057(02)00762-1.
Nicotine and ethanol are the most widely abused drugs in the world. They are very often used and abused together. However, little is known about the functional interaction of nicotine and ethanol. The current project studied the interactive effects of nicotine and ethanol on working memory in the eight-arm radial maze. Adult female rats were trained on a radial arm maze for 18 sessions to reach asymptotic levels of choice accuracy. During the maintenance phase of radial arm maze testing, which indexed working memory function, the rats were injected with nicotine (0, 0.15, 0.3, 0.6, and 1.2 mg/kg sc, 20 min before testing) with and without ethanol pretreatment (0 or 1.5 g/kg, 16% v/v ip, 30 min before testing). All animals received the treatments in a counterbalanced order with at least 1 week between treatments. Higher doses of nicotine had a significant interaction with ethanol in terms of radial arm maze choice accuracy. Nicotine plus ethanol coadministration precipitated a significant choice accuracy impairment at doses that when given alone had no effect on performance. At the lower dose range of nicotine, ethanol coadministration eliminated the nicotine-induced memory improvement. No significant effects were seen with either nicotine or ethanol treatment or their interaction on response latency in the radial arm maze. The nicotine-ethanol interactive effects on memory were compared with the interaction of their well-characterized hypothermic effects. Nicotine and alcohol, when injected separately or in combination, induced hypothermia with no significant interactive effect. This study found that ethanol blocked low-dose nicotine-induced memory improvement and precipitated memory impairment with high-dose nicotine treatment. This interaction may be an important consideration for nicotine and ethanol coabuse and the possible therapeutic use of nicotinic drugs for memory dysfunction.
尼古丁和乙醇是世界上滥用最为广泛的药物。它们经常被同时使用和滥用。然而，关于尼古丁和乙醇的功能相互作用却知之甚少。当前项目研究了尼古丁和乙醇对八臂辐射状迷宫中工作记忆的交互作用。成年雌性大鼠在辐射状迷宫上接受18次训练，以达到选择准确性的渐近水平。在作为工作记忆功能指标的辐射状迷宫测试的维持阶段，大鼠在测试前20分钟皮下注射尼古丁（0、0.15、0.3、0.6和1.2毫克/千克），同时有或没有乙醇预处理（0或1.5克/千克，16%体积/体积腹腔注射，测试前30分钟）。所有动物均以平衡顺序接受治疗，每次治疗之间至少间隔1周。就辐射状迷宫选择准确性而言，较高剂量的尼古丁与乙醇存在显著的相互作用。尼古丁与乙醇联合给药在单独给药时对行为表现无影响的剂量下，会导致显著的选择准确性受损。在尼古丁的低剂量范围内，乙醇联合给药消除了尼古丁诱导的记忆改善。尼古丁或乙醇治疗及其相互作用对辐射状迷宫中的反应潜伏期均无显著影响。将尼古丁-乙醇对记忆的交互作用与其已充分表征的体温过低效应的交互作用进行了比较。尼古丁和酒精单独或联合注射时均会引起体温过低，且无显著的交互作用。本研究发现，乙醇会阻断低剂量尼古丁诱导的记忆改善，并在高剂量尼古丁治疗时导致记忆受损。这种相互作用可能是尼古丁和乙醇共同滥用以及烟碱类药物用于记忆功能障碍可能的治疗用途时的一个重要考虑因素。
