Cocaine Is Low on the Value Ladder of Rats: Possible Evidence for Resilience to Addiction
Cocaine Is Low on the Value Ladder of Rats: Possible Evidence for Resilience to Addiction
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DOI：
10.1371/journal.pone.0011592
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发表时间：
2010-07-28
期刊：
影响因子：
3.7
通讯作者：
Ahmed, Serge H.
中科院分区：
文献类型：
--
作者：
Cantin, Lauriane;Lenoir, Magalie;Ahmed, Serge H.
背景：评估可卡因的相对价值以及它如何随长期药物使用而变化是成瘾研究的长期目标。令人惊讶的是，最近在老鼠身上的实验--到目前为止该领域最常用的动物模型--表明可卡因的价值比之前认为的要低。方法/主要发现：这里我们报告了一系列选择性实验，这些实验更好地定义了可卡因在老鼠价值阶梯上的相对位置(即，不同奖励的偏好排序)。老鼠被允许选择服用可卡因或饮用加糖精的水--这是一种非药物替代品，在生物学上不是必需的。通过系统地改变甜水的成本和浓度，我们发现可卡因在大多数老鼠的价值阶梯上很低，接近甜水的最低浓度。此外，对过去5年所有实验的回顾分析表明，无论过去可卡因使用多么严重，大多数大鼠都很容易放弃可卡因使用，转而使用非药物替代。只有少数人，不到15%，在过去最严重的可卡因使用水平下，继续服用可卡因，即使在饥饿的情况下，并提供一种可以缓解他们对卡路里需求的天然糖。结论/意义：这种结果模式(大多数大鼠戒除可卡因；少数大鼠更喜欢可卡因)很好地映射了人类可卡因成瘾的流行病学，表明只有少数大鼠容易受到可卡因成瘾的影响，而大多数大鼠在广泛使用毒品的情况下仍具有弹性。长期以来，人们一直怀疑人类对药物成瘾的适应能力，但无法确定，主要是因为很难对药物自身暴露和/或人类吸毒者可获得性的差异进行追溯控制。这一结论对可卡因成瘾的临床前神经生物学研究和未来的药物开发具有重要的意义。
Background: Assessing the relative value of cocaine and how it changes with chronic drug use represents a long-standing goal in addiction research. Surprisingly, recent experiments in rats - by far the most frequently used animal model in this field - suggest that the value of cocaine is lower than previously thought.Methodology/Principal Findings: Here we report a series of choice experiments that better define the relative position of cocaine on the value ladder of rats (i.e., preference rank-ordering of different rewards). Rats were allowed to choose either taking cocaine or drinking water sweetened with saccharin - a nondrug alternative that is not biologically essential. By systematically varying the cost and concentration of sweet water, we found that cocaine is low on the value ladder of the large majority of rats, near the lowest concentrations of sweet water. In addition, a retrospective analysis of all experiments over the past 5 years revealed that no matter how heavy was past cocaine use most rats readily give up cocaine use in favor of the nondrug alternative. Only a minority, fewer than 15% at the heaviest level of past cocaine use, continued to take cocaine, even when hungry and offered a natural sugar that could relieve their need of calories.Conclusions/Significance: This pattern of results (cocaine abstinence in most rats; cocaine preference in few rats) maps well onto the epidemiology of human cocaine addiction and suggests that only a minority of rats would be vulnerable to cocaine addiction while the large majority would be resilient despite extensive drug use. Resilience to drug addiction has long been suspected in humans but could not be firmly established, mostly because it is difficult to control retrospectively for differences in drug self-exposure and/or availability in human drug users. This conclusion has important implications for preclinical research on the neurobiology of cocaine addiction and for future medication development.