Dommett Eleanor J
Brain and Behavioural Sciences, Dept of Life, Health and Chemical Sciences, Biomedical Research Network, The Open University, Walton Hall, Milton Keynes, MK7 6AA, UK.
Pharmacol Biochem Behav. 2014 Sep;124:196-203. doi: 10.1016/j.pbb.2014.06.001. Epub 2014 Jun 14.
Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder and is normally treated with either stimulant or non-stimulant medication such as methylphenidate and atomoxetine respectively. The impact of these drugs on attention and impulsivity has been explored extensively in healthy animals but there is little research into their effects in an animal model of ADHD. In the present study we investigated the effects of both drugs on the spontaneously hypertensive rat (SHR) model of ADHD using the five-choice serial reaction time task (5CSRTT). We found a number of difficulties associated with training this vulnerable strain on such a complex task. However, where rats were able to learn the task we found very small effects of methylphenidate; increased incorrect responding and therefore decreased accuracy, a marker of attention at a single dose. There were no significant effects of atomoxetine on accuracy once multiple comparisons were taken into consideration. We found no effects of either drug on premature responding, a marker of impulsivity. These results indicate that the 5CSRTT may not be most sensitive to the impulsivity displayed in the SHR. Furthermore, they suggest that the SHR may lack predictive validity and further investigation is needed to optimise use of this model.
注意力缺陷多动障碍(ADHD)是最常见的神经发育障碍,通常分别使用兴奋剂或非兴奋剂药物进行治疗,如哌甲酯和托莫西汀。这些药物对注意力和冲动性的影响在健康动物中已得到广泛研究,但在ADHD动物模型中的效果研究较少。在本研究中,我们使用五选择连续反应时任务(5CSRTT)研究了这两种药物对ADHD自发性高血压大鼠(SHR)模型的影响。我们发现,在如此复杂的任务上训练这种易受影响的品系存在一些困难。然而,在大鼠能够学会该任务的情况下,我们发现哌甲酯的影响非常小;单次给药时错误反应增加,因此准确性降低,准确性是注意力的一个指标。考虑多次比较后,托莫西汀对准确性没有显著影响。我们发现这两种药物对过早反应(冲动性的一个指标)均无影响。这些结果表明,5CSRTT可能对SHR中表现出的冲动性不是最敏感的。此外,它们表明SHR可能缺乏预测效度,需要进一步研究以优化该模型的使用。