Rats classified as low or high cocaine locomotor responders: a unique model involving striatal dopamine transporters that predicts cocaine addiction-like behaviors.
Rats classified as low or high cocaine locomotor responders: a unique model involving striatal dopamine transporters that predicts cocaine addiction-like behaviors.
复制标题
被分类为低或高可卡因运动反应者的大鼠：一种涉及纹状体多巴胺转运蛋白的独特模型，可预测可卡因成瘾样行为。
DOI：
10.1016/j.neubiorev.2013.07.002
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发表时间：
2013
影响因子：
8.2
通讯作者：
Zahniser,NancyR
中科院分区：
文献类型：
--
作者：
Yamamoto,DorothyJ;Nelson,AnnaM;Mandt,BruceH;Larson,GaynorA;Rorabaugh,JackiM;Ng,ChristopherMC;Barcomb,KelseyM;Richards,ToniL;Allen,RichardM;Zahniser,NancyR
个体差异是药物成瘾的一个标志。在这里，我们描述了一个大鼠模型的基础上差异的初始反应低剂量可卡因。尽管相似的大脑可卡因水平，个别远系繁殖的Sprague-Dawley大鼠表现出明显不同的幅度的急性可卡因诱导的运动活动，从而，可以被归类为低或高可卡因反应（LCR或HCR）。LCR和HCR的不同之处在于药物诱导的多动症，而不是新奇相关的多动症。LCR具有较高的基础数量的纹状体多巴胺转运体（DAT）比HCR和表现出边际可卡因抑制ofin vivoDAT活性和可卡因诱导的细胞外DA的增加。重要的是，较低的初始可卡因反应预测更大的运动敏感性，条件性位置偏好和更大的动机，自我管理可卡因低剂量收购。此外，与HCR相比，被归类为LCR的远交Long-Evans大鼠对可卡因的歧视性刺激效应更敏感。总体而言，LCR/HCR模型的结果强调了纹状体DAT对初始可卡因反应性个体差异的贡献，以及评估初始药物反应对随后成瘾样行为表达的影响的价值。
Individual differences are a hallmark of drug addiction. Here, we describe a rat model based on differential initial responsiveness to low dose cocaine. Despite similar brain cocaine levels, individual outbred Sprague-Dawley rats exhibit markedly different magnitudes of acute cocaine-induced locomotor activity and, thereby, can be classified as low or high cocaine responders (LCRs or HCRs). LCRs and HCRs differ in drug-induced, but not novelty-associated, hyperactivity. LCRs have higher basal numbers of striatal dopamine transporters (DATs) than HCRs and exhibit marginal cocaine inhibition ofin vivoDAT activity and cocaine-induced increases in extracellular DA. Importantly, lower initial cocaine response predicts greater locomotor sensitization, conditioned place preference and greater motivation to self-administer cocaine following low dose acquisition. Further, outbred Long-Evans rats classified as LCRs, versus HCRs, are more sensitive to cocaine's discriminative stimulus effects. Overall, results to date with the LCR/HCR model underscore the contribution of striatal DATs to individual differences in initial cocaine responsiveness and the value of assessing the influence of initial drug response on subsequent expression of addiction-like behaviors.