Department of Pharmacology, Federal University of São Paulo, Brazil.
Addict Biol. 2011 Oct;16(4):565-79. doi: 10.1111/j.1369-1600.2011.00341.x. Epub 2011 Jul 25.
Repeated or even a single exposure to drugs of abuse can lead to persistent locomotor sensitization, which is the result of an abundance of neuroplastic changes occurring within the circuitry involved in motivational behavior and is thought to play a key role in certain aspects of drug addiction. There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy that is increasingly being used as a cognitive enhancer and has been proposed as a pharmacotherapy for cocaine dependence. Male mice were used to investigate the ability of modafinil to induce locomotor sensitization after repeated or single administration in mice. Bidirectional cross-sensitization with cocaine and modafinil-induced conditioned place preference were also evaluated. Both repeated and single exposure to moderate and high doses of modafinil produced a pronounced locomotor sensitization that cross-sensitized in a bidirectional way with cocaine. Remarkably, when cocaine and modafinil were repeatedly administered sequentially, their behavioral sensitization was additive. Supporting these behavioral sensitization data, modafinil produced a pronounced conditioned place preference in the mouse. Taken together, the present findings provide pre-clinical evidence for the addictive potential of modafinil. Our data also strongly suggest that similar neural substrates are involved in the psychomotor/rewarding effects of modafinil and cocaine.
反复甚至单次接触滥用药物会导致持续的运动敏化，这是参与动机行为的电路中发生大量神经可塑性变化的结果，被认为在药物成瘾的某些方面发挥关键作用。关于莫达非尼（一种用于治疗嗜睡症的促醒药物）的成瘾潜力存在很大争议，莫达非尼越来越多地被用作认知增强剂，并被提议作为可卡因依赖的药物治疗。雄性小鼠被用于研究莫达非尼在重复或单次给药后诱导运动敏化的能力。还评估了可卡因和莫达非尼诱导的条件性位置偏好的双向交叉敏化。重复和单次接触中等到高剂量的莫达非尼都会产生明显的运动敏化，与可卡因呈双向交叉敏化。值得注意的是，当可卡因和莫达非尼反复顺序给药时，它们的行为敏化是相加的。支持这些行为敏化数据，莫达非尼在小鼠中产生了明显的条件性位置偏好。总之，这些发现为莫达非尼的成瘾潜力提供了临床前证据。我们的数据还强烈表明，在莫达非尼和可卡因的精神运动/奖励作用中涉及相似的神经基质。
