Neuroscience Graduate Program, University of Washington, Seattle, WA, USA.
Center for Integrative Brain Research, Seattle Children's Research Institute, 1900 Ninth Ave., Seattle, WA, 98101, USA.
Psychopharmacology (Berl). 2020 Jan;237(1):55-68. doi: 10.1007/s00213-019-05349-2. Epub 2019 Aug 28.
Comorbid use of heroin and cocaine is highly prevalent among drug users and can greatly increase addiction risk. Nonetheless, little is known regarding how a multi-drug history impacts motivation and cue responsivity to individual drugs.
We used behavioral-economic procedures to examine motivation to maintain drug consumption and tests of drug-seeking to drug-associated cues to assess sensitivity to heroin and cocaine-associated cues in rats that had a self-administration history of heroin, cocaine, or both drugs.
Unexpectedly, we found that groups with a polydrug history of heroin and cocaine did not have higher levels of motivation or cue-induced reinstatement of drug-seeking for either cocaine or heroin compared to single drug groups. Nonetheless, we did find drug-specific differences in both economic price and cue sensitivity. Specifically, demand elasticity was lower for cocaine compared to heroin in animals with a single drug history, but not with polydrug groups. In addition, cocaine demand was predictive of the degree of cue-induced reinstatement of drug-seeking for cocaine following extinction, whereas heroin demand was predictive of the degree of reactivity to a heroin-associated cue. Furthermore, although cue reactivity following the initial self-administration phase did not differ across cues and drug history, reactivity to both heroin and cocaine cues was greater during subsequent heroin use compared to cocaine use, and this enhanced reactivity to heroin cues persisted during forced abstinence.
These results indicate that there is a greater motivation to maintain cocaine consumption, but higher sensitivity to drug-associated cues with a history of heroin use, suggesting that cocaine and heroin may drive continued drug use through different behavioral processes.
在吸毒者中，同时使用海洛因和可卡因的现象非常普遍，这极大地增加了成瘾的风险。尽管如此，对于多药使用史如何影响个体药物的动机和线索反应性，人们知之甚少。
我们使用行为经济学程序来检查维持药物消费的动机，并测试药物寻求对与药物相关的线索的反应，以评估对有海洛因、可卡因或两者药物自我给药史的大鼠对海洛因和可卡因相关线索的敏感性。
出乎意料的是，我们发现，有海洛因和可卡因多药使用史的组与单一药物组相比，对可卡因或海洛因的动机或线索诱导的药物寻求复吸没有更高的水平。尽管如此，我们确实发现了两种药物在经济价格和线索敏感性方面的特异性差异。具体而言，在有单一药物史的动物中，可卡因的需求弹性低于海洛因，但在多药组中则不然。此外，可卡因的需求可以预测可卡因在消退后线索诱导的药物寻求复吸的程度，而海洛因的需求可以预测对海洛因相关线索的反应程度。此外，尽管在初始自我给药阶段之后，线索反应性在不同的线索和药物史之间没有差异，但在随后的海洛因使用期间，对海洛因和可卡因线索的反应性更大，这种对海洛因线索的增强反应性在强制禁欲期间仍然存在。
这些结果表明，有更强的动机来维持可卡因的消费，但对海洛因使用史的药物相关线索的敏感性更高，这表明可卡因和海洛因可能通过不同的行为过程驱动持续的药物使用。
