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小鼠反复接触咖啡因和酒精后的致敏作用与耐受性

Sensitization and Tolerance Following Repeated Exposure to Caffeine and Alcohol in Mice.

作者信息

May Christina E, Haun Harold L, Griffin William C

机构信息

Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Science, Medical University of South Carolina, Charleston, South Carolina.

出版信息

Alcohol Clin Exp Res. 2015 Aug;39(8):1443-52. doi: 10.1111/acer.12794. Epub 2015 Jul 2.

DOI:10.1111/acer.12794
PMID:26136115
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4515142/
Abstract

BACKGROUND

Energy drinks are popular mixers with alcohol. While energy drinks contain many ingredients, caffeine is an important pharmacologically active component and is generally present in larger amounts than in other caffeinated beverages. In these studies, we investigated the hypothesis that caffeine would influence the effects of alcohol (ethanol [EtOH]) on conditioned taste aversion (CTA), ataxia, and locomotor activity (LA) after repeated exposure.

METHODS

Four groups of mice were exposed by oral gavage twice daily to vehicle, EtOH (4 g/kg), caffeine (15 mg/kg), or the EtOH/caffeine combination. CTA to saccharin and ataxia in the parallel rod task was evaluated after 8 or 16 gavages, respectively, using EtOH (1 to 3 g/kg) or EtOH/caffeine (3 mg/kg + 2 g/kg) challenges. In addition, LA was evaluated initially and after repeated exposure to oral gavage of these drugs and doses.

RESULTS

Repeated oral gavage of EtOH produced significant locomotor sensitization, with those mice increasing total distance traveled by 2-fold. The locomotor response to caffeine, while significantly greater than vehicle gavage, did not change with repeated exposure. On the other hand, repeated gavage of caffeine/EtOH combination produced a substantial increase in total distance traveled after repeated exposure (~4-fold increase). After repeated EtOH exposure, there was significant tolerance to EtOH in the CTA and parallel rod tests. However, neither a history of caffeine exposure nor including caffeine influenced EtOH-induced CTA. Interestingly, a history of caffeine exposure increased the ataxic response to the caffeine/EtOH combination and appeared to reduce the ataxic response to high doses of EtOH.

CONCLUSIONS

The data support the general hypothesis that repeated exposure to caffeine influences the response to EtOH. Together with previously published work, these data indicate that caffeine influences some EtOH-related behaviors, notably locomotion and ataxia, but appears not to influence the expression of conditioned behaviors.

摘要

背景

能量饮料是与酒精混合饮用的常见饮品。虽然能量饮料含有多种成分,但咖啡因是一种重要的药理活性成分,其含量通常比其他含咖啡因的饮料更高。在这些研究中,我们探讨了咖啡因是否会影响酒精(乙醇[EtOH])对反复接触后条件性味觉厌恶(CTA)、共济失调和运动活动(LA)的影响这一假设。

方法

将四组小鼠每天经口灌胃两次,分别给予溶剂、乙醇(4 g/kg)、咖啡因(15 mg/kg)或乙醇/咖啡因组合。分别在灌胃8次或16次后,使用乙醇(1至3 g/kg)或乙醇/咖啡因(3 mg/kg + 2 g/kg)激发,评估对糖精的CTA以及平行杆试验中的共济失调情况。此外,在最初以及反复经口灌胃这些药物和剂量后评估LA。

结果

反复经口灌胃乙醇可产生显著的运动敏化,这些小鼠的总行进距离增加了2倍。对咖啡因的运动反应虽然显著大于溶剂灌胃,但反复接触后并未改变。另一方面,反复灌胃咖啡因/乙醇组合在反复接触后使总行进距离大幅增加(约增加4倍)。反复接触乙醇后,在CTA和平行杆试验中对乙醇产生了显著耐受性。然而,既往的咖啡因接触史以及加入咖啡因均未影响乙醇诱导的CTA。有趣的是,咖啡因接触史增加了对咖啡因/乙醇组合的共济失调反应,并且似乎降低了对高剂量乙醇的共济失调反应。

结论

数据支持反复接触咖啡因会影响对乙醇反应的总体假设。与先前发表的研究结果一起,这些数据表明咖啡因会影响一些与乙醇相关的行为,尤其是运动和共济失调,但似乎不影响条件性行为的表现。

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