Lile Joshua A
Department of Behavioral Science, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Exp Clin Psychopharmacol. 2006 Feb;14(1):20-33. doi: 10.1037/1064-1297.14.1.20.
Illicit use of psychostimulants, such as cocaine and methamphetamine, continues to pose a significant public health concern. On the basis of the relative success at treating opiate and tobacco users with agonist substitution treatments, this strategy has been pursued in the search for a pharmacotherapy for psychostimulant addiction. The reinforcing effects of drugs are central to their abuse liability; therefore, gaining a better understanding of the factors that determine the reinforcing effects of psychostimulants should inform the development of an effective treatment. Although the reinforcing effects of drugs are known to be multiply determined, the author's dissertation research focused on pharmacological factors. This review presents results from that research as well as findings reported in the extant literature, suggesting that the reinforcing effects of psychostimulant drugs are determined both by their pharmacodynamic and pharmacokinetic profiles. There is evidence to support the conclusion that affinity for dopamine transporters appears to be of critical importance, whereas serotonin transporters seem to serve a modulatory function. A more rapid rate of onset may enhance a drug's reinforcing effects, but a drug with a slow onset can still maintain self-administration. A drug's duration of action may only influence the rate but not the strength of responding that is maintained. Slow-onset, long-acting monoamine transporter ligands can be expected to have reinforcing effects and therefore abuse liability, which has implications for the use of these drugs as pharmacotherapies. Nonetheless, on the basis of promising preclinical and clinical findings, this appears to represent a viable treatment strategy.
非法使用精神兴奋剂，如可卡因和甲基苯丙胺，仍然是一个重大的公共卫生问题。基于在使用激动剂替代疗法治疗阿片类药物和烟草使用者方面取得的相对成功，人们一直在寻求用这种策略来寻找治疗精神兴奋剂成瘾的药物疗法。药物的强化作用是其滥用可能性的核心；因此，更好地了解决定精神兴奋剂强化作用的因素应该有助于开发有效的治疗方法。虽然已知药物的强化作用是由多种因素决定的，但作者的博士论文研究集中在药理学因素上。这篇综述介绍了该研究的结果以及现有文献中报道的研究结果，表明精神兴奋剂药物的强化作用是由其药效学和药代动力学特征共同决定的。有证据支持这样的结论，即对多巴胺转运体的亲和力似乎至关重要，而5-羟色胺转运体似乎起调节作用。起效更快可能会增强药物的强化作用，但起效慢的药物仍能维持自我给药。药物的作用持续时间可能只影响维持反应的速率，而不影响其强度。起效慢、作用时间长的单胺转运体配体有望具有强化作用，因此具有滥用可能性，这对将这些药物用作药物疗法有影响。尽管如此，基于有前景的临床前和临床研究结果，这似乎代表了一种可行的治疗策略。
