Department of Psychiatry, University of California San Diego, La Jolla, California, USA.
Biol Psychiatry. 2010 Apr 15;67(8):784-7. doi: 10.1016/j.biopsych.2009.12.015. Epub 2010 Feb 4.
Modafinil is prescribed for the treatment of narcolepsy. It has been postulated that modafinil might treat cognitive disruption in neuropsychiatric disorders. The mechanisms underlying such modafinil-induced improvements in performance have yet to be delineated however. Recent evidence suggests that modafinil might block the dopamine transporter (DAT) and that the dopamine D1 receptor (D1R) might contribute to modafinil effects.
Dopamine D1R wildtype (WT), heterozygous (HT), and knockout (KO) mice received vehicle, modafinil, or the selective DAT blocker GBR12909 in a progressive ratio breakpoint study.
Both modafinil and GBR12909 increased motivation in the task as measured by an increase in breakpoint in WT and HT mice. These drug-induced increases in motivation were reduced in dopamine D1R HT mice relative to their WT littermates. The D1R KO mice did not respond in the task.
These data support the hypothesis that modafinil increases motivation. Moreover, given the similarity of effects with GBR12909, the data corroborate evidence that the behavioral effects of modafinil might be due to DAT inhibition. Furthermore, the dopamine D1R might play a downstream role in mediating modafinil-induced increases in motivation. Thus, studies reporting cognition-enhancing effects of modafinil might have been influenced by its ability to increase motivation.
莫达非尼被开处方用于治疗嗜睡症。有人推测，莫达非尼可能治疗神经精神障碍的认知障碍。然而，其性能改善的潜在机制尚未阐明。最近的证据表明，莫达非尼可能会阻断多巴胺转运体（DAT），而多巴胺 D1 受体（D1R）可能有助于莫达非尼的作用。
多巴胺 D1R 野生型（WT）、杂合子（HT）和敲除（KO）小鼠在逐步比率突破试验中接受载体、莫达非尼或选择性 DAT 阻滞剂 GBR12909。
莫达非尼和 GBR12909均增加了 WT 和 HT 小鼠任务中的动机，表现为突破点增加。与 WT 同窝仔相比，这些药物诱导的动机增加在多巴胺 D1R HT 小鼠中减少。D1R KO 小鼠在任务中没有反应。
这些数据支持了莫达非尼增加动机的假设。此外，鉴于与 GBR12909 的相似效应，数据证实了莫达非尼的行为效应可能是由于 DAT 抑制。此外，多巴胺 D1R 可能在介导莫达非尼诱导的动机增加中发挥下游作用。因此，报告莫达非尼增强认知作用的研究可能受到其增加动机能力的影响。
