School of Life Sciences, P.O. Box 874501, Arizona State University, Tempe, AZ 85287-4501, USA.
Neuropharmacology. 2014 Jan;76 Pt B(0 0):301-19. doi: 10.1016/j.neuropharm.2013.08.014. Epub 2013 Aug 23.
Addiction to psychostimulants, including cocaine and amphetamine, is associated with dysregulation of dopamine and serotonin (5-HT) neurotransmitter systems. Neuroadaptations in these systems vary depending on the stage of the drug taking-abstinence-relapse cycle. Consequently, the effects of potential treatments that target these systems may vary depending on whether they are given during abstinence or relapse. In this review, we discuss evidence that dopamine D3 receptors (D3Rs) and 5-HT1B receptors (5-HT1BRs) are dysregulated in response to both chronic psychostimulant use and subsequent abstinence. We then review findings from preclinical self-administration models which support targeting D3Rs and 5-HT1BRs as potential medications for psychostimulant dependence. Potential side effects of the treatments are discussed and attention is given to studies reporting positive treatment outcomes that depend on: 1) whether testing occurs during self-administration versus abstinence, 2) whether escalation of drug self-administration has occurred, 3) whether the treatments are given repeatedly, and 4) whether social factors influence treatment outcomes. We conclude that D3/D2 agonists may decrease psychostimulant intake; however, side effects of D3/D2R full agonists may limit their therapeutic potential, whereas D3/D2R partial agonists have fewer undesirable side effects. D3-selective antagonists may not reduce psychostimulant intake during relapse, but nonetheless, may decrease motivation for seeking psychostimulants with relatively few side-effects. 5-HT1BR agonists provide a striking example of treatment outcomes that are dependent on the stage of the addiction cycle. Specifically, these agonists initially increase cocaine's reinforcing effects during maintenance of self-administration, but after a period of abstinence they reduce psychostimulant seeking and the resumption of self-administration. In conclusion, we suggest that factors contributing to dysregulation of monoamine systems, including drug history, abstinence, and social context, should be considered when evaluating potential treatments to better model treatment effects in humans. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.
对包括可卡因和安非他命在内的精神兴奋剂的成瘾与多巴胺和 5-羟色胺（5-HT）神经递质系统的失调有关。这些系统的神经适应性变化取决于药物使用-戒断-复发周期的阶段。因此，针对这些系统的潜在治疗方法的效果可能会有所不同，具体取决于它们是在戒断期间还是在复发期间使用。在这篇综述中，我们讨论了证据表明，多巴胺 D3 受体（D3R）和 5-HT1B 受体（5-HT1BR）在慢性使用精神兴奋剂和随后的戒断后都会失调。然后，我们回顾了临床前自我给药模型的研究结果，这些结果支持将 D3R 和 5-HT1BR 作为治疗精神兴奋剂依赖的潜在药物。讨论了潜在的治疗副作用，并关注了报告阳性治疗结果的研究，这些结果取决于：1）测试是在自我给药期间还是在戒断期间进行，2）是否发生了药物自我给药的升级，3）治疗是否反复进行，以及 4）社会因素是否影响治疗结果。我们的结论是，D3/D2 激动剂可能会减少精神兴奋剂的摄入；然而，D3/D2R 完全激动剂的副作用可能会限制其治疗潜力，而 D3/D2R 部分激动剂的副作用较少。D3 选择性拮抗剂可能不会减少复发期间精神兴奋剂的摄入，但尽管如此，它们可能会减少对精神兴奋剂的动机，而副作用相对较少。5-HT1BR 激动剂提供了一个依赖于成瘾周期阶段的治疗结果的显著例子。具体来说，这些激动剂在维持自我给药期间最初会增加可卡因的强化作用，但在一段时间的戒断后，它们会减少对精神兴奋剂的寻求和自我给药的恢复。总之，我们建议在评估潜在治疗方法时，应考虑导致单胺系统失调的因素，包括药物史、戒断和社会背景，以更好地模拟人类的治疗效果。本文是题为“NIDA 40 周年特刊”的特刊的一部分。
