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首页> 外文期刊>The European Journal of Neuroscience >Demand elasticity predicts addiction endophenotypes and the therapeutic efficacy of an orexin/hypocretin-1 receptor antagonist in rats
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Demand elasticity predicts addiction endophenotypes and the therapeutic efficacy of an orexin/hypocretin-1 receptor antagonist in rats

机译：需求弹性预测成瘾的内骨型和orexin / hypocretin-1受体拮抗剂在大鼠中的治疗效果

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Behavioral economics is a powerful, translational approach for measuring drug demand in both humans and animals. Here, we asked if demand for cocaine in rats with limited drug experience could be used to identify individuals most at risk of expressing an addiction phenotype following either long- or intermittent access self-administration schedules, both of which model the transition to uncontrolled drug-seeking. Because the orexin-1 receptor antagonist SB-334867 (SB) is particularly effective at reducing drug-seeking in highly motivated individuals, we also asked whether demand measured after prolonged drug experience could predict SB efficacy. Demand elasticity (alpha) measured immediately following acquisition of cocaine self-administration ('baseline alpha') was positively correlated with alpha assessed after 2w of long- or intermittent access. Baseline alpha also predicted the magnitude of compulsive responding for cocaine, drug-seeking in initial abstinence and cued reinstatement following long-, intermittent- or standard short access. When demand was measured after these differential access conditions, alpha predicted the same addiction endophenotypes predicted by baseline alpha, as well as primed reinstatement and the emergence of negative emotional mood behavior following abstinence. alpha also predicted the efficacy of SB, such that high demand rats showed greater reductions in motivation for cocaine following SB compared to low demand rats. Together, these findings indicate that alpha might serve as a behavioral biomarker to predict individuals most likely to progress from controlled to uncontrolled drug use, and to identify individuals most likely to benefit from orexin-based therapies for the treatment of addiction.
机译：行为经济是一种强大的翻译方法，可在人类和动物中测量药物需求。在这里，我们询问有限药物经验的大鼠的可卡因需求可用于鉴定最多表达患者的患者的患者，这些型在长期或间歇性接入自我管理时间表之后，这两者都可以将过渡到不受控制的药物 - 寻求。因为orexin-1受体拮抗剂SB-334867（SB）在减少高度动机的个体中，尤为有效地降低毒药，我们还询问是否在长期药物经验后测量的需求可以预测SB功效。在获取可卡因自我给药后立即测量的需求弹性（α）与长或间歇性接入后2W后评估的alpha呈正相关。基线alpha还预测了可卡因的强迫响应的大小，在初始禁欲中寻找药物，并且在长期间，间歇或标准的短途通道之后追逐恢复。当在这些差分接入条件下测量需求时，alpha预测了基线α预测的相同的成瘾内型，以及禁止症状后的引发恢复以及负面情绪行为的出现。 α还预测了Sb的功效，使得高需求大鼠与低需求大鼠相比，在Sb之后的可卡因的动机效果表现出更大的抑制。这些发现表明，α可能是行为生物标志物，以预测最有可能从控制到不受控制的药物使用的人，并且鉴定最容易受益于基于orexin的疗法的个体，以便治疗成瘾。

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