Higgins Guy A, Silenieks Leo B, Van Niekerk Annalise, Desnoyer Jill, Patrick Amy, Lau Winnie, Thevarkunnel Sandy
InterVivo Solutions Inc., 120 Carlton Street, Toronto, ON Canada M5A 4K2; Dept. Pharmacology & Toxicology, U. Toronto, ON, Canada M5S 1A8.
InterVivo Solutions Inc., 120 Carlton Street, Toronto, ON Canada M5A 4K2.
Behav Brain Res. 2015 Jun 1;286:347-55. doi: 10.1016/j.bbr.2015.02.050. Epub 2015 Mar 5.
The present study investigated the impact of a spared nerve injury (SNI) on the daily performance of rats tested in two instrumental conditioning procedures: the progressive ratio (PR) schedule of food reinforcement to study motivation for an appetitive stimulus, and the 5-choice serial reaction time task (5-CSRTT), a test of attention and reaction time. Separate groups of male, Sprague-Dawley rats of age 8-10 months were trained to asymptotic performance in either task, before undergoing either SNI or sham surgery. After a recovery period of 3-4 days the animals were run 5 days/week for 3 months in either task. Tests of responsivity to evoked tactile (Von Frey) and thermal (acetone) stimuli were also conducted over this period to check integrity of the model. Post SNI surgery, rats showed equivalent responding to sham controls for food available under a PR schedule throughout the test period, implying a similar level of motivation for a food reward. In contrast, a performance deficit emerged in SNI treated rats run in the 5-CSRTT, consistent with an attentional deficit. This deficit emerged during the second month post-surgery and was characterized by slower response speed, reduced accuracy and increased trial omissions. Both SNI groups showed equivalent hypersensitivity to evoked sensory stimuli compared to controls. Since attention based deficits have been reported in individuals with clinical forms of neuropathic pain, the present studies suggest a novel approach to study this phenomena and a means to study the effect of treatments against this cognitive endpoint.
本研究调查了保留神经损伤(SNI)对大鼠在两种操作性条件反射程序中的日常行为表现的影响:用于研究对食欲刺激的动机的食物强化渐进比率(PR)时间表,以及用于测试注意力和反应时间的5选串行反应时间任务(5-CSRTT)。将8至10个月大的雄性Sprague-Dawley大鼠分成不同组,在接受SNI手术或假手术之前,对它们进行其中一项任务的训练,直至达到渐近表现。经过3至4天的恢复期后,动物们每周进行5天、为期3个月的其中一项任务测试。在此期间,还对诱发的触觉(von Frey)和热(丙酮)刺激的反应性进行了测试,以检查模型的完整性。SNI手术后,在整个测试期间,大鼠在PR时间表下对可获得食物的反应与假手术对照组相当,这意味着对食物奖励的动机水平相似。相比之下,在5-CSRTT中进行测试的SNI处理大鼠出现了行为表现缺陷,这与注意力缺陷一致。这种缺陷在手术后第二个月出现,其特征是反应速度减慢、准确性降低和遗漏试验增加。与对照组相比,两个SNI组对诱发的感觉刺激均表现出同等程度的超敏反应。由于在患有临床形式神经性疼痛的个体中已报告存在基于注意力的缺陷,本研究提出了一种研究此现象的新方法以及一种研究针对这一认知终点的治疗效果的手段。