While preclinical work has aimed to outline the neural mechanisms of drug addiction, it has overwhelmingly focused on male subjects. There has been a push in recent years to incorporate females into existing addiction models; however, males and females often have different behavioral strategies, making it important to not only include females, but to develop models that assess the factors that comprise female drug addiction. Traditional self-administration models often include light or tone cues that serve as discriminative stimuli and/or consequent stimuli, making it nearly impossible to disentangle the effects of cue learning, the cues themselves, and acute effects of psychostimulant drugs. To disentangle the interaction between drug-associated cues and the consummatory and appetitive responding driven by cocaine, we have developed a new behavioral procedure that combines Pavlovian-instrumental transfer with behavioral economic analysis. This task can be completed within a single session, allowing for studies looking at estrous cycle stage-dependent effects in intact cycling females, something that has been difficult in the past. In this study, we found no differences in self-administration across the estrous cycle in the absence of cues; however, when cues were introduced, the cues that acquired value during estrus-but not during diestrus or in males-increased motivation. Cues paired during estrus also increased c-fos expression to a greater extent in striatal regions, an effect that may underlie the observed increases in seeking induced by these cues, even weeks later. Together, these data suggest that fundamental differences in the motivational properties of psychostimulant drugs between males and females are complex and are driven primarily by the interaction between drug-associated stimuli and drug effects.

中文翻译：

---

线索在发情周期依赖性增强可卡因强化中起着关键作用。

虽然临床前工作旨在概述药物成瘾的神经机制，但它绝大多数都集中在男性受试者身上。近年来一直在推动将女性纳入现有的成瘾模型；然而，男性和女性通常有不同的行为策略，因此不仅要包括女性，而且要开发模型来评估构成女性吸毒成瘾的因素，这一点很重要。传统的自我管理模型通常包括用作辨别刺激和/或后续刺激的光或音调提示，这使得几乎不可能区分提示学习的效果、提示本身和精神兴奋剂药物的急性作用。解开药物相关线索与可卡因驱动的完成和食欲反应之间的相互作用，我们开发了一种新的行为程序，将巴甫洛夫工具转移与行为经济分析相结合。这项任务可以在一次会议中完成，从而可以研究研究完整骑车女性的发情周期阶段依赖性影响，这在过去一直很困难。在这项研究中，我们发现在没有提示的情况下，整个发情周期的自我管理没有差异；然而，当引入线索时，在发情期间获得价值的线索——而不是在发情间期或雄性中——增加了动机。在发情期间配对的线索也在纹状体区域更大程度上增加了 c-fos 表达，这种效应可能是观察到的由这些线索诱导的寻求增加的基础，甚至在几周后也是如此。一起，