Translation of drug targets from preclinical studies to clinical trials has been aided by cross-species behavioral tasks, but evidence for brain-based engagement during task performance is still required. Cross-species progressive ratio breakpoint tasks (PRBTs) measure motivation-related behavior and are pharmacologically and clinically sensitive. We recently advanced elevated parietal alpha power as a cross-species electroencephalographic (EEG) biomarker of PRBT engagement. Given that amphetamine increases breakpoint in mice, we tested its effects on breakpoint and parietal alpha power in both humans and mice. Twenty-three healthy participants performed the PRBT with EEG after amphetamine or placebo in a double-blind design. C57BL/6J mice were trained on PRBT with EEG (n = 24) and were treated with amphetamine or vehicle. A second cohort of mice was trained on PRBT without EEG (n = 40) and was treated with amphetamine or vehicle. In humans, amphetamine increased breakpoint. In mice, during concomitant EEG, 1 mg/kg of amphetamine significantly decreased breakpoint. In cohort 2, however, 0.3 mg/kg of amphetamine increased breakpoint consistent with human findings. Increased alpha power was observed in both species as they reached breakpoint, replicating previous findings. Amphetamine did not affect alpha power in either species. Amphetamine increased effort in humans and mice. Consistent with previous reports, elevated parietal alpha power was observed in humans and mice as they performed the PRBT. Amphetamine did not affect this EEG biomarker of effort. Hence, these findings support the pharmacological predictive validity of the PRBT to measure effort in humans and mice and suggest that this EEG biomarker is not directly reflective of amphetamine-induced changes in effort.

药物靶标从临床前研究到临床试验的转化得到了跨物种行为任务的帮助，但仍然需要任务执行期间基于大脑的参与的证据。跨物种渐进比率断点任务 (PRBT) 测量与动机相关的行为，并且具有药理学和临床敏感性。我们最近将顶叶 α 功率升高作为 PRBT 参与的跨物种脑电图 (EEG) 生物标志物。鉴于安非他明会增加小鼠的断点，我们测试了它对人类和小鼠的断点和顶叶 α 功率的影响。在双盲设计中，23 名健康参与者在服用安非他明或安慰剂后进行了脑电图 PRBT 治疗。 C57BL/6J 小鼠接受 PRBT 和 EEG 训练（n = 24），并接受安非他明或媒介物治疗。第二组小鼠接受了无脑电图 PRBT 训练（n = 40），并接受安非他明或媒介物治疗。在人类中，安非他明会增加断点。在小鼠中，在同时进行脑电图检查时，1 mg/kg 的安非他明显着降低了断点。然而，在第 2 组中，0.3 毫克/千克的安非他明增加了断点，这与人类研究结果一致。当两个物种达到断点时，我们都观察到阿尔法功率增加，重复了之前的发现。安非他明不会影响这两个物种的阿尔法能量。安非他明会增加人类和小鼠的努力程度。与之前的报告一致，在人类和小鼠进行 PRBT 时观察到顶叶 α 功率升高。安非他明不会影响这种努力程度的脑电图生物标志物。 因此，这些发现支持 PRBT 测量人类和小鼠努力程度的药理学预测有效性，并表明这种脑电图生物标志物并不直接反映安非他明引起的努力变化。