抗多巴胺β-羟化酶-皂草素选择性耗竭皮质去甲肾上腺素会损害大鼠的注意力功能，并增强胍法辛的作用。
Selective depletion of cortical noradrenaline by anti-dopamine beta-hydroxylase-saporin impairs attentional function and enhances the effects of guanfacine in the rat.
作者信息
Milstein Jean A, Lehmann Olivia, Theobald David E H, Dalley Jeffrey W, Robbins Trevor W
机构信息
Department of Experimental Psychology, University of Cambridge Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
出版信息
Psychopharmacology (Berl). 2007 Jan;190(1):51-63. doi: 10.1007/s00213-006-0594-x. Epub 2006 Nov 10.
RATIONALE
Previous data indicate that depletion of cortical noradrenaline (NA) impairs performance of an attentional five-choice serial reaction time task (5CSRT) under certain conditions. This study employed a novel immunotoxin, anti-dopamine-beta hydroylase (DbetaH)-saporin, to make relatively selective lesions of the noradrenergic projections to the prefrontal cortex (PFC) in rats trained to perform the 5CSRT.
OBJECTIVES
The aim of this work is to examine (1) the effect of cortical noradrenaline depletion on sustained attentional performance in the 5CSRT under a variety of test conditions and (2) the effects of guanfacine, a selective alpha-2 adrenoceptor agonist on attentional performance in sham and NA-depleted rats.
MATERIALS AND METHODS
Animals received either intramedial prefrontal anti-DbetaH-saporin or vehicle and were tested on the baseline task with a variety of additional manipulations including (1) decreasing target duration, (2) increasing rate and (3) temporal unpredictability of target presentation and (4) systemic guanfacine.
RESULTS
Anti-DbetaH-saporin infused into the PFC produced a substantial loss of DbetaH-positive fibers in that region and in other adjacent cortical areas. There was no significant depletion of DA or 5-HT. NA-depleted animals were not impaired on the baseline task, but were slower to respond correctly under high event rate conditions, and their discriminative accuracy was reduced when stimulus predictability decreased. Guanfacine significantly reduced discriminative accuracy in NA-depleted animals only.
CONCLUSION
Selective cortical NA depletion produced deficits on the 5CSRT test of sustained attention, especially when the attentional load was increased and in response to systemic guanfacine. These results are consistent with a role of coeruleo-cortical NA in the regulation of effortful attentional processes.
理论依据
先前的数据表明，在某些条件下，皮质去甲肾上腺素（NA）的耗竭会损害注意力五选择连续反应时任务（5CSRT）的表现。本研究采用一种新型免疫毒素，抗多巴胺-β羟化酶（DbetaH）-皂草素，对经过训练执行5CSRT的大鼠前额叶皮质（PFC）的去甲肾上腺素能投射进行相对选择性损伤。
目的
本研究旨在检验（1）在各种测试条件下，皮质NA耗竭对5CSRT中持续注意力表现的影响，以及（2）选择性α-2肾上腺素能受体激动剂胍法辛对假手术组和NA耗竭大鼠注意力表现的影响。
材料与方法
动物接受内侧前额叶抗DbetaH-皂草素或赋形剂处理，并在基线任务上进行测试，包括多种额外操作，如（1）缩短目标持续时间，（2）提高速率，（3）目标呈现的时间不可预测性，以及（4）全身性胍法辛。
结果
注入PFC的抗DbetaH-皂草素导致该区域及其他相邻皮质区域DbetaH阳性纤维大量丧失。多巴胺（DA）或5-羟色胺（5-HT）无明显耗竭。NA耗竭的动物在基线任务上未受损，但在高事件率条件下正确反应较慢，且当刺激可预测性降低时，其辨别准确性降低。胍法辛仅显著降低了NA耗竭动物的辨别准确性。
结论
选择性皮质NA耗竭在持续注意力的5CSRT测试中产生缺陷，尤其是当注意力负荷增加以及对全身性胍法辛产生反应时。这些结果与蓝斑-皮质NA在调节努力注意力过程中的作用一致。
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