Rodefer Joshua S, Nguyen Tuyet N
Department of Psychology, University of Iowa, E11 Seashore Hall, Iowa, City, IA 52242-1407, USA.
Neurobiol Aging. 2008 Feb;29(2):309-13. doi: 10.1016/j.neurobiolaging.2006.10.005. Epub 2006 Nov 13.
We evaluated young (3-4 months) and aged (22-24 months) male Sprague-Dawley rats in an attentional set-shifting procedure that assessed reversal, intradimensional shift (IDS), and extradimensional shift (EDS) discrimination learning tasks within one test session. These aspects of discrimination learning are sensitive to damage to distinct regions of frontal cortex. Compared to young animals, aged rats were significantly impaired on the EDS task and did not demonstrate significant impairment on the reversal or IDS tasks. The opioid antagonist naltrexone (2mg/kg, ip) was administered to young and aged rats prior to testing to assess possible improvements in aged-related cognitive impairments. Naltrexone (2mg/kg) attenuated the impairments in cognitive function in the EDS task for aged animals, but did not alter any task performance in the younger group. These results suggest that normal aging in rats is associated with impaired medial frontal cortex function as assessed by this attentional set-shifting procedure and opioid mediated mechanisms may represent a therapeutic target for drugs to improve cognitive deficits associated with aging.
我们在一个注意力转换程序中评估了年轻（3 - 4个月）和老年（22 - 24个月）雄性Sprague-Dawley大鼠，该程序在一次测试中评估了反转、维度内转换（IDS）和维度间转换（EDS）辨别学习任务。辨别学习的这些方面对额叶皮质不同区域的损伤很敏感。与年轻动物相比，老年大鼠在EDS任务上显著受损，而在反转或IDS任务上未表现出显著损伤。在测试前，给年轻和老年大鼠注射阿片类拮抗剂纳曲酮（2mg/kg，腹腔注射），以评估其对与年龄相关的认知障碍可能的改善作用。纳曲酮（2mg/kg）减轻了老年动物在EDS任务中的认知功能损伤，但未改变年轻组的任何任务表现。这些结果表明，通过这种注意力转换程序评估，大鼠的正常衰老与内侧额叶皮质功能受损有关，阿片类介导的机制可能是改善与衰老相关认知缺陷药物的治疗靶点。
