Study of the addictive potential of modafinil in naive and cocaine-experienced rats
Study of the addictive potential of modafinil in naive and cocaine-experienced rats
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DOI：
10.1007/s00213-002-1080-8
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发表时间：
2002-06-01
影响因子：
3.4
通讯作者：
Piazza, PV
中科院分区：
文献类型：
--
作者：
Deroche-Gamonet, V;Darnaudéry, M;Piazza, PV
理由：莫达非尼是一种促进清醒的药物，因此用于治疗嗜睡症和嗜睡症。临床前和临床研究表明，莫达非尼对有药物经验的受试者可能具有微弱的增强作用。然而，尽管莫达非尼的可用性最近有所增加，但其在未曾用药的健康个体中的滥用可能性仍然完全未经调查。目的：我们研究的目的是通过测试莫达非尼对幼鼠的增强作用来研究莫达非尼的潜在成瘾特性。还测试了莫达非尼与可卡因增强作用的相互作用。方法：首先，使用静脉注射。通过自我给药和场所条件反射测试，我们研究了大范围剂量的莫达非尼对幼鼠的强化和奖励作用。其次，我们在接受可卡因自我给药训练的大鼠中测试了莫达非尼对可卡因的增强和激励作用的影响。将莫达非尼的作用与安非他明和氟哌啶醇的作用进行了比较。结果：莫达非尼不会产生强化或奖励作用，也不会改变可卡因的作用。结论：我们的结果表明，莫达非尼对初次接触者不具有成瘾潜力。此外，它在行为上与经典的中枢神经系统兴奋剂不同，众所周知，经典的中枢神经系统兴奋剂会改变可卡因引起的作用。然而，正如之前在非人类灵长类动物和人类中所显示的那样，莫达非尼可能对有可卡因经历的个体具有增强作用。
Rationale: Modafinil is a drug that promotes wakefulness and, as such, is used to treat hypersomnia and narcolepsy. Preclinical and clinical studies suggest that modafinil could possess weak reinforcing effects in drug-experienced subjects. However, its abuse potential in drug-naive healthy individuals is still totally uninvestigated, despite the fact that availability of modafinil has recently increased. Objectives: The purpose of our study was to investigate the potential addictive properties of modafinil by testing its reinforcing effects in naive rats. The interactions of modafinil with the reinforcing effects of cocaine were also tested. Methods: First, using i.v. self-administration and place conditioning tests, we studied the reinforcing and rewarding effects of a large range of doses of modafinil in naive rats. Second, we tested the influence of modafinil on reinforcing and incentive effects of cocaine in rats trained for cocaine self-administration. The effects of modafinil were compared with those of amphetamine and haloperidol. Results: Modafinil did not produce reinforcing or rewarding effects and did not modify the effects of cocaine. Conclusions: Our results suggest that modafinil does not possess an addictive potential in naive individuals. Furthermore, it would be behaviorally distinct from classical central nervous system stimulants which are known to alter cocaine-induced effects. However, as shown previously in nonhuman primates and in humans, modafinil could possibly have reinforcing effects in cocaine-experienced individuals.