Choosing Under the Influence: A Drug-Specific Mechanism by Which the Setting Controls Drug Choices in Rats
Choosing Under the Influence: A Drug-Specific Mechanism by Which the Setting Controls Drug Choices in Rats
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DOI：
10.1038/npp.2015.195
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发表时间：
2016-01-01
影响因子：
7.6
通讯作者：
Ahmed, Serge H.
中科院分区：
文献类型：
--
作者：
Vandaele, Youna;Cantin, Lauriane;Ahmed, Serge H.
大量证据表明，环境可以控制人类和动物的药物选择。在这里，我们揭示了在大鼠中，这种控制的一个主要机制涉及到在选择时对其他竞争选项的药物影响的调节。简单地说，在两种不同的环境中，给大鼠提供药物剂量（可卡因或海洛因）和短暂接触糖精甜味水的选择。在一种情况下，在影响下选择是不可能的，老鼠在很大程度上更喜欢糖精而不是可卡因或海洛因。相比之下，当同样的老鼠被转移到一个可以在影响下选择的环境中时，它们选择药物的方式是非排他性的，还是排他性的，分别取决于药物是增强还是抑制了甜蜜的奖励。因此，当大鼠在选择时处于海洛因的食欲影响下时，它们更频繁地选择糖精与海洛因交替。相反，当老鼠受到可卡因的强烈影响时，它们不再选择糖精，而是继续只服用可卡因。这些设置和药物特异性的偏好变化是快速和可逆的，可以诱导被动管理可卡因或海洛因之前的选择。最后，老鼠表现得好像它们对药物对其选择的影响视而不见。这种行为可以解释为什么老鼠在药物影响下做出选择的环境中，特别是如果这种影响排除了其他重要的选择，或者相反，增强了有害的选择，那么老鼠很容易伤害自己，有时甚至会死亡。
Ample evidence shows that the setting can control drug choices in both humans and animals. Here we reveal in rats that a major mechanism of this control involves a regulation of the drug influence on other competing options at the time of choice. Briefly, rats were offered a choice between a drug dose (cocaine or heroin) and a brief access to water sweetened with saccharin in two different settings. In one setting, choosing under the influence was not possible and rats largely preferred saccharin over either cocaine or heroin. In contrast, when the same rats were shifted to a setting where choosing under the influence was possible, they chose the drug either nonexclusively or exclusively depending on whether the drug enhanced or suppressed sweet reward, respectively. Thus, when rats were under the orexigenic influence of heroin at the time of choice, they more frequently chose saccharin in alternation with heroin. In contrast, when rats were under the anorexic influence of cocaine, they stopped choosing saccharin and continued taking cocaine exclusively. These setting-and drug-specific changes in preference were rapid and reversible, and could be induced by passively administering cocaine or heroin before choice. Finally, rats behaved as if they were oblivious to the drug influence on their choices. This behavior could explain why rats are vulnerable to harm themselves, sometimes to the point of death, in settings where choices are made under the drug influence, notably if this influence excludes other important options or, conversely, enhances harmful ones.