Carr Madison R, van Mourik Yvar, Gómez-Sotres Paula, Solinas Marcello, de Vries Taco J, Pattij Tommy
Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam University Medical Center, location VU Medical Center, Amsterdam, The Netherlands.
Laboratory of Experimental and Clinical Neurosciences, INSERM U1084, University of Poitiers, Poitiers, France.
Behav Brain Res. 2025 Mar 5;480:115405. doi: 10.1016/j.bbr.2024.115405. Epub 2024 Dec 18.
Modelling delay discounting behavior in rodents is important for understanding the neurobiological mechanisms underlying cognitive control and associated impulsivity disorders. Conventional rodent delay discounting procedures require extensive training and frequent experimenter interaction, as rodents are tested in separate operant chambers away from their home cage. To address these limitations, we adapted and characterize here a self-adjusting delay discounting procedure to an automated CombiCage setup. Rodents were trained during the most active phase of the light-dark cycle, completing 120 trials daily. During each session, we measured large reward preference, mean adjusted delay, and trial participation across multiple delays. Results showed that rodents exhibited discounting behavior after two weeks, with performance stability increasing at 7 weeks training with delay. We also evaluated the influence of altering the consecutive choice criteria (ccc), number of trial choices for a delay step to adjust up or down. Lower ccc (3 vs 8) increased both the number of delay steps encountered per session and task participation. Additionally, we examined the effects of pharmacological interventions, including the psychostimulant amphetamine and the dopamine D1 receptor antagonist, SCH23390. A high dose amphetamine reduced preference for large immediate and short delayed rewards and decreased the mean adjusted delay in a non-dose dependent manner, while SCH23390 did not affect task performance. Together, this novel automated self-adjusting procedure enables high-throughput collection of delay discounting data, with potential applications for investigating impulsivity across the lifespan. However, the current extended session design may limit its suitability for pharmacological evaluations.
对啮齿动物的延迟折扣行为进行建模，对于理解认知控制及相关冲动性障碍背后的神经生物学机制非常重要。传统的啮齿动物延迟折扣程序需要大量训练以及实验者频繁互动，因为啮齿动物是在远离其饲养笼的单独操作箱中接受测试的。为了解决这些局限性，我们在此将一种自我调整的延迟折扣程序应用于自动化组合笼设置并进行了表征。啮齿动物在明暗周期最活跃的阶段接受训练，每天完成120次试验。在每个实验环节中，我们测量了对大额奖励的偏好、平均调整延迟以及多个延迟条件下的试验参与度。结果显示，啮齿动物在两周后表现出折扣行为，随着延迟训练7周，表现稳定性增加。我们还评估了改变连续选择标准（ccc）的影响，即延迟步骤向上或向下调整时试验选择的次数。较低的ccc（3对8）增加了每个实验环节中遇到的延迟步骤数量和任务参与度。此外，我们研究了药物干预的效果，包括精神兴奋剂苯丙胺和多巴胺D1受体拮抗剂SCH23390。高剂量苯丙胺降低了对大额即时和短延迟奖励的偏好，并以非剂量依赖的方式降低了平均调整延迟，而SCH23390不影响任务表现。总之，这种新颖的自动化自我调整程序能够高通量收集延迟折扣数据，在研究全生命周期的冲动性方面具有潜在应用。然而，当前的延长实验环节设计可能会限制其在药物评估方面的适用性。
