Interactions between modafinil and cocaine during the induction of conditioned place preference and locomotor sensitization in mice: implications for addiction.
Interactions between modafinil and cocaine during the induction of conditioned place preference and locomotor sensitization in mice: implications for addiction.
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DOI：
10.1016/j.bbr.2012.07.039
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发表时间：
2012-12-01
影响因子：
2.7
通讯作者：
Anagnostaras SG
中科院分区：
文献类型：
--
作者：
Shuman T;Cai DJ;Sage JR;Anagnostaras SG
莫达非尼是一种促进清醒的药物，可有效提高警觉性和注意力，具有各种批准和标签外应用。莫达非尼的机制尚不清楚，但初步研究表明滥用潜力有限。然而，最近的一些出版物表明，莫达非尼在某些条件下是有益的。本研究采用小鼠条件性位置偏爱和运动敏感性评价莫达非尼的强化作用。实验1研究了高剂量的莫达非尼（75 mg/kg）及其与可卡因（15 mg/kg）的相互作用。单独使用可卡因和莫达非尼与可卡因联合给药可诱导自发活动的敏化;单独使用莫达非尼几乎或没有自发敏化。单独给予莫达非尼、单独给予可卡因以及莫达非尼加可卡因的动物表现出强烈且大致相当的位置偏好。当使用低激发剂量的莫达非尼进行致敏试验时，在所有可卡因预处理的小鼠中观察到交叉致敏。实验2检查了低剂量的莫达非尼，该剂量与给予人类的剂量相似，并已显示出在小鼠中产生认知增强。低剂量莫达非尼（0.75 mg/kg）不产生条件性位置偏爱或运动敏感化。总之，这些结果表明，莫达非尼有可能产生奖励，特别是在可卡因成瘾者中，应该谨慎使用。然而，典型的低剂量给药可能会缓和这些影响，并可能解释人类缺乏成瘾性。
Modafinil is a wake-promoting drug effective at enhancing alertness and attention with a variety of approved and off-label applications. The mechanism of modafinil is not well understood but initial studies indicated a limited abuse potential. A number of recent publications, however, have shown that modafinil can be rewarding under certain conditions. The present study assessed the reinforcing properties of modafinil using conditioned place preference and locomotor sensitization in mice. Experiment 1 examined a high dose of modafinil (75 mg/kg) as well as its interactions with cocaine (15 mg/kg). Cocaine alone and modafinil co-administered with cocaine induced sensitization of locomotor activity; modafinil alone showed little or no locomotor sensitization. Animals given modafinil alone, cocaine alone, and modafinil plus cocaine exhibited a strong and roughly equivalent place preference. When tested for sensitization using a low challenge dose of modafinil, cross-sensitization was observed in all cocaine-pretreated mice. Experiment 2 examined a low dose of modafinil that is similar to the dose administered to humans and has been shown to produce cognitive enhancements in mice. Low dose modafinil (0.75 mg/kg) did not produce conditioned place preference or locomotor sensitization. Together, these results suggest that modafinil has the potential to produce reward, particularly in cocaine addicts, and should be used with caution. However, the typical low dose administered likely moderates these effects and may account for lack of addiction seen in humans.