Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.
Mol Pharmacol. 2014 Apr;85(4):640-50. doi: 10.1124/mol.113.090118. Epub 2014 Feb 5.
Psychostimulants, such as cocaine and amphetamines, act primarily through the monoamine neurotransmitters dopamine (DA), norepinephrine, and serotonin. Although stimulant addiction research has largely focused on DA, medication development efforts targeting the dopaminergic system have thus far been unsuccessful, leading to alternative strategies aimed at abating stimulant abuse. Noradrenergic compounds have shown promise in altering the behavioral effects of stimulants in rodents, nonhuman primates, and humans. In this review, we discuss the contribution of each adrenergic receptor (AR) subtype (α1, α2, and β) to five stimulant-induced behaviors relevant to addiction: locomotor activity, conditioned place preference, anxiety, discrimination, and self-administration. AR manipulation has diverse effects on these behaviors; each subtype profoundly influences outcomes in some paradigms but is inconsequential in others. The functional neuroanatomy and intracellular signaling mechanisms underlying the impact of AR activation/blockade on these behaviors remain largely unknown, presenting a new frontier for research on psychostimulant-AR interactions.
精神兴奋剂，如可卡因和安非他命，主要通过单胺神经递质多巴胺（DA）、去甲肾上腺素和血清素起作用。尽管兴奋剂成瘾研究主要集中在 DA 上，但针对多巴胺能系统的药物开发努力迄今为止并未成功，导致采取了旨在减轻兴奋剂滥用的替代策略。去甲肾上腺素能化合物在改变啮齿动物、非人灵长类动物和人类中兴奋剂的行为效应方面显示出希望。在这篇综述中，我们讨论了每种肾上腺素能受体（AR）亚型（α1、α2 和 β）对与成瘾相关的五种兴奋剂诱导行为的贡献：运动活动、条件性位置偏好、焦虑、辨别和自我给药。AR 操作对这些行为有不同的影响；每种亚型在某些范式中对结果有深远影响，但在其他范式中则无关紧要。AR 激活/阻断对这些行为的影响的功能神经解剖学和细胞内信号转导机制在很大程度上仍然未知，为研究精神兴奋剂-AR 相互作用提供了新的前沿。
