Stoffel Erin C, Cunningham Kathryn A
Center for Addiction Research, Department of Pharmacology and Toxicology, University of Texas Medical Branch, 300 University Boulevard, Galveston, TX 77555-1031, USA.
Drug Alcohol Depend. 2008 Jan 1;92(1-3):69-78. doi: 10.1016/j.drugalcdep.2007.06.012. Epub 2007 Nov 9.
Behavioral disinhibition, a component of impulsivity, has been associated with cocaine abuse and dependence. To examine the relationship between behavioral disinhibition and vulnerability to cocaine use disorders, we employed the high responder (HR)/low responder (LR) rodent model, in which rats that exhibit high levels of activity in response to a novel environment are more sensitive to the effects of psychostimulants. In Experiment 1, performance under a differential reinforcement of low-rate (DRL) schedule was used as a measure of behavioral disinhibition in HR and LR rats. The HR rats displayed more behavioral disinhibition relative to LR rats on the DRL 20- and 35-s schedules. In Experiment 2, rats were divided into groups with high disinhibition (HD) and low disinhibition (LD) based on DRL 20-s performance, then challenged with cocaine. Rats characterized as HD and LD had similar DRL 20-s performance to rats characterized as HR and LR (Experiment 1), respectively, but did not differ in their response to cocaine. The results of this study suggest that the HR phenotype may also be characterized by greater behavioral disinhibition, and that the DRL task is a suitable animal model to investigate the role of behavioral disinhibition in vulnerability to the behavioral effects of cocaine.
行为去抑制作为冲动性的一个组成部分,与可卡因滥用及成瘾有关。为了研究行为去抑制与可卡因使用障碍易感性之间的关系,我们采用了高反应者(HR)/低反应者(LR)啮齿动物模型,在此模型中,对新环境表现出高活动水平的大鼠对精神兴奋剂的作用更敏感。在实验1中,低速率差异强化(DRL)程序下的表现被用作衡量HR和LR大鼠行为去抑制的指标。在DRL 20秒和35秒程序中,HR大鼠相对于LR大鼠表现出更多的行为去抑制。在实验2中,根据DRL 20秒的表现将大鼠分为高去抑制(HD)组和低去抑制(LD)组,然后用可卡因进行挑战。被归类为HD和LD的大鼠在DRL 20秒的表现分别与被归类为HR和LR的大鼠(实验1)相似,但它们对可卡因的反应没有差异。本研究结果表明,HR表型可能也具有更强的行为去抑制特征,并且DRL任务是研究行为去抑制在可卡因行为效应易感性中作用的合适动物模型。