The activity-regulated cytoskeleton-associated protein (Arc, also known as Arg3.1), an immediate early gene and synaptic regulator, is upregulated following a single cocaine exposure. However, there is not much known regarding Arc/Arg3.1's potential contribution to addiction-relevant behaviors. Despite known learning and memory deficits in contextual fear and water-maze reversal learning tasks, we find that mice lacking Arc/Arg3.1 perform conditioned place preference and operant conditioning involving positive reinforcers (food and cocaine) with little-to-no impairment. However, following normal saline-extinction, wild type (WT) mice show a classic inverted-U dose-response function, while Arc/Arg3.1 knockout (KO) mice fail to adjust their intake across multiple doses. Importantly, Arc/Arg3.1 KO and WT mice behave comparably on an increasing cost task (FR1-FR3; acquisition dose), providing evidence that both groups find cocaine reinforcing. Differences in individuals that drive variations in use patterns and particularly, drug intake levels, are critical as they influence the likelihood of developing dependence. Our data suggest that Arc/Arg3.1 may contribute to addiction as a regulator of drug-taking vulnerability under different drug availability conditions.

一次单独的可卡因暴露后，活性调节的细胞骨架相关蛋白（Arc，也称为Arg3.1），一种直接的早期基因和突触调节剂，被上调。但是，关于Arc / Arg3.1对成瘾相关行为的潜在贡献知之甚少。尽管已知在上下文恐惧和水迷宫逆转学习任务中的学习和记忆缺陷，但我们发现缺少Arc / Arg3.1的小鼠执行条件化位置偏好和操作性条件化，涉及到正强化剂（食物和可卡因），几乎没有损害。但是，在正常的生理盐水消灭之后，野生型（WT）小鼠表现出经典的倒U剂量反应功能，而Arc / Arg3.1敲除（KO）小鼠无法跨多个剂量调整其摄入量。重要的是，Arc / Arg3.1 KO和WT小鼠在增加成本的任务（FR1-FR3；获取剂量）上表现可比，提供了两组都发现可卡因增强的证据。导致使用模式（尤其是药物摄入量）变化的个人差异至关重要，因为它们会影响发展依赖性的可能性。我们的数据表明，在不同的药物供应条件下，Arc / Arg3.1可能作为成瘾性的调节剂，促进成瘾。