Interactive effects of methylphenidate and alcohol on discrimination, conditioned place preference and motor coordination in C57BL/6J mice.
Interactive effects of methylphenidate and alcohol on discrimination, conditioned place preference and motor coordination in C57BL/6J mice.
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DOI：
10.1007/s00213-012-2849-z
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发表时间：
2013-02
影响因子：
3.4
通讯作者：
Patrick, Kennerly S.
中科院分区：
文献类型：
--
作者：
Griffin, William C., III;McGovern, Robin W.;Bell, Guinevere H.;Randall, Patrick K.;Middaugh, Lawrence D.;Patrick, Kennerly S.
关键词：
先前的研究表明哌醋甲酯 (MPH) 和酒精（乙醇，EtOH）相互作用会显着影响人类和小鼠的反应。目前的研究验证了 MPH 和 EtOH 相互作用以增强小鼠乙醇相关行为的假设。我们使用了几种行为任务，包括：MPH 训练和 EtOH 训练的小鼠中的药物辨别、条件位置偏好 (CPP)、旋转杆和平行杆装置。我们还使用气相色谱法测量脑组织中 EtOH 和 MPH 的 d 和 l 异构体以及代谢物哌乙酯 (EPH) 的水平。在辨别中，EtOH (1g/kg) 使 MPH 训练的小鼠的 MPH 泛化曲线 (1-2mg/kg) 产生显着的左移，但没有观察到 MPH (0.625-1.25mg/kg) 对 EtOH 训练的小鼠 (0-2.5g/kg) 的 EtOH 辨别力产生影响。在 CPP 中，与载体 (30.7%) 相比，MPH (1.25mg/kg) 和 EtOH (1.75g/kg) 组合显着增加了药物配对侧的时间，但这与 MPH (28.8%) 和 EtOH (33.6%) 相似。在平行杆装置中测量的脚滑误差表明该药物组合非常共济失调，与 EtOH 相比，脚滑增加了 29.5%。最后，1.75g/kg EtOH 与 1.25mg/kg MPH 组合并未改变脑部 EtOH 浓度。然而，EtOH 显着增加 d-MPH 和 l-EPH，而不改变 l-MPH 脑浓度。 EtOH 与 MPH 结合时行为效应的增强可能是由于大脑 d-MPH 浓度的选择性增加。这些研究与人类对药物组合的内感受意识增强的观察结果一致，并提供了关于该药物组合增强共济失调作用的新的临床观点。
Prior research indicates methylphenidate (MPH) and alcohol (ethanol, EtOH) interact to significantly affect responses humans and mice. The present studies tested the hypothesis that MPH and EtOH interact to potentiate ethanol-related behaviors in mice. We used several behavioral tasks including: drug discrimination in MPH-trained and EtOH-trained mice, conditioned place preference (CPP), rota-rod and the parallel rod apparatus. We also used gas chromatographic methods to measure brain tissue levels of EtOH and the d and l isomers of MPH and the metabolite, ethylphenidate (EPH). In discrimination, EtOH (1g/kg) produced a significant leftward shift in the MPH generalization curve (1-2mg/kg) for MPH-trained mice, but no effects of MPH (0.625-1.25mg/kg) on EtOH discrimination in EtOH-trained mice (0-2.5g/kg) were observed. In CPP, the MPH (1.25mg/kg) and EtOH (1.75g/kg) combination significantly increased time on the drug paired side compared to vehicle (30.7%), but this was similar to MPH (28.8%) and EtOH (33.6%). Footslip errors measured in a parallel rod apparatus indicated that the drug combination was very ataxic, with footslips increasing 29.5% compared to EtOH. Finally, brain EtOH concentrations were not altered by 1.75g/kg EtOH combined with 1.25mg/kg MPH. However, EtOH significantly increased d-MPH and l-EPH without changing l-MPH brain concentrations. The enhanced behavioral effects when EtOH is combined with MPH are likely due to the selective increase in brain d-MPH concentrations. These studies are consistent with observations in humans of increased interoceptive awareness of the drug combination and provide new clinical perspectives regarding enhanced ataxic effects of this drug combination.
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DOI：
10.1124/jpet.106.108795
发表时间：
2006-11-01
影响因子：
3.5
作者：
Becker, Howard C.;Baros, Alicia M.
通讯作者：
Baros, Alicia M.
影响因子：
3.4
作者：
Cunningham, Christopher L.;Patel, Priya
通讯作者：
Patel, Priya
影响因子：
1.6
作者：
Crissman, AM;Studders, SL;Becker, HC
通讯作者：
Becker, HC
DOI：
10.1016/j.jchromb.2007.11.030
发表时间：
2008-02-01
影响因子：
3
作者：
LeVasseur, Natalie L.;Zhu, Hao-Jie;Patrick, Kennerly S.
通讯作者：
Patrick, Kennerly S.
影响因子：
10.6
作者：
Kuczenski, R;Segal, DS
通讯作者：
Segal, DS