Understanding the mechanisms underpinning individual variance in addiction vulnerability requires the development of validated, high-throughput screens. In a prior study of a large sample of male isogenic C57BL/6J mice, the direction and magnitude of methamphetamine (MA)-induced place-conditioning predicts the propensity to acquire oral MA self-administration, as well as the efficacy of MA to serve as a reinforcer. The present study examined whether or not such a predictive relationship also exists in females. Adult C57BL/6J females underwent a 4-day MA place-conditioning paradigm (once daily injections of 2 mg/kg) and were then trained to nose-poke for delivery of a 20 mg/L MA solution under increasing schedules of reinforcement, followed by dose-response testing (5−400 mg/L MA). Akin to males, 53 % of the females exhibited a conditioned place-preference, while 32 % of the mice were MA-neutral and 15 % exhibited a conditioned place-aversion. However, unlike males, the place-conditioning phenotype did not transfer to MA-reinforced nose-poking behavior under operant-conditioning procedures, with 400 mg/L MA intake being inversely correlated place-conditioning. While only one MA-conditioning dose has been assayed to date, these data indicate that sex does not significantly shift the proportion of C57BL/6J mice that perceive MA’s interoceptive effects as positive, neutral or aversive. However, a sex difference appears to exist regarding the predictive relationship between the motivational valence of MA and subsequent drug-taking behavior; females exhibit MA-taking behavior and reinforcement, despite their initial perception of the stimulant interoceptive effects as positive, neutral or negative.

了解成瘾易感性个体差异的机制需要开发经过验证的高通量筛选。在先前对大量雄性同基因 C57BL/6J 小鼠样本的研究中，甲基苯丙胺 (MA) 诱导的位置调节的方向和幅度预测了获得口服 MA 自我给药的倾向，以及 MA 的效力作为强化剂。本研究检查了女性是否也存在这种预测关系。成年 C57BL/6J 女性接受了为期 4 天的 MA 位置调节范例（每天注射一次 2 mg/kg），然后被训练在增加强化计划的情况下用鼻子戳以提供 20 mg/L MA 溶液，随后通过剂量反应测试 (5–400 mg/L MA)。与男性相似，53% 的雌性表现出条件性地点偏好，而 32% 的小鼠是 MA 中性，15% 表现出条件性地点厌恶。然而，与男性不同，位置调节表型在操作性调节程序下并未转移到 MA 增强的戳鼻子行为，400 mg/L MA 摄入量与位置调节呈负相关。虽然迄今为止只测定了一种 MA 调节剂量，但这些数据表明，性别不会显着改变 C57BL/6J 小鼠的比例，这些小鼠将 MA 的内感受效应视为积极的、中性的或厌恶的。然而，关于 MA 的动机效价与随后的吸毒行为之间的预测关系，似乎存在性别差异。女性表现出接受 MA 的行为和强化，