Liu Shijing, Heitz Richard P, Bradberry Charles W
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
J Neurosci Methods. 2009 Feb 15;177(1):67-72. doi: 10.1016/j.jneumeth.2008.09.020. Epub 2008 Oct 2.
Among a range of cognitive deficits, human cocaine addicts display increased impulsivity and decreased performance monitoring. In order to establish an animal model that can be used to study the underlying neurobiology of these deficits associated with addiction, we have developed a touch screen based Stop Signal Response Task for rhesus monkeys. This task is essentially identical to the clinically used Stop Signal Task employed for diagnostic and research purposes. In this task, impulsivity is reflected in the amount of time needed to inhibit a response after it has been initiated, the Stop Signal Response Time (SSRT). Performance monitoring is reflected by the slowing of response times following Stop trials (Post-Stop Slowing, PSS). Herein we report on the task structure, the staged methods for training animals to perform the task, and a comparison of performance values for control and cocaine experienced animals. Relative to controls, monkeys that had self-administered cocaine, followed by 18 months abstinence, displayed increased impulsivity (increased SSRT values), and decreased performance monitoring (decreased PSS values). Our results are consistent with human data, and thereby establish an ideal animal model for studying the etiology and underlying neurobiology of cocaine-induced impulse control and performance monitoring deficits.
在一系列认知缺陷中,人类可卡因成瘾者表现出冲动性增加和执行监控能力下降。为了建立一种可用于研究与成瘾相关的这些缺陷的潜在神经生物学机制的动物模型,我们为恒河猴开发了一种基于触摸屏的停止信号反应任务。该任务与临床上用于诊断和研究目的的停止信号任务基本相同。在这个任务中,冲动性体现在启动反应后抑制反应所需的时间量上,即停止信号反应时间(SSRT)。执行监控通过停止试验后反应时间的减慢来体现(停止后减慢,PSS)。在此,我们报告该任务的结构、训练动物执行任务的分阶段方法,以及对照动物和有可卡因使用经历的动物的表现值比较。与对照组相比,自行注射可卡因后戒断18个月的猴子表现出冲动性增加(SSRT值增加)和执行监控能力下降(PSS值降低)。我们的结果与人类数据一致,从而建立了一个理想的动物模型,用于研究可卡因诱导的冲动控制和执行监控缺陷的病因及潜在神经生物学机制。