Zajo Kristin N, Fadel Jim R, Burk Joshua A
Department of Psychology, College of William & Mary, Williamsburg, VA, 23187, USA.
Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC, 29208, USA.
Psychopharmacology (Berl). 2016 Feb;233(4):639-47. doi: 10.1007/s00213-015-4139-z. Epub 2015 Nov 4.
Orexins are neuropeptides released in multiple brain regions from neurons that originate within the lateral hypothalamus and contiguous perfornical area. The basal forebrain, a structure implicated in attentional processing, receives orexinergic inputs. Our previous work demonstrated that administration of an orexin-1 receptor antagonist, SB-334867, systemically or via infusion directly into the basal forebrain, can disrupt performance in a task that places explicit demands on attentional processing.
Given that the orexin-1 receptor binds orexin A with high affinity, we tested whether orexin A could enhance attention in rats.
Attentional performance was assessed using a task that required discrimination of variable duration visual signals from trials when no signal was presented. We also tested whether infusions of orexin A into the lateral ventricle could attenuate deficits following lesions of medial prefrontal cortical cholinergic projections that arise from the basal forebrain.
Infusions of orexin A into the basal forebrain attenuated distracter-induced decreases in attentional performance. Orexin A attenuated deficits in lesioned animals when a visual distracter was presented.
The present results support the view that orexin A can enhance attentional performance via actions in the basal forebrain and may be beneficial for some conditions characterized by attentional dysfunction due to disruption of cortical cholinergic inputs.
食欲素是由起源于下丘脑外侧和毗邻的穹窿周区的神经元在多个脑区释放的神经肽。基底前脑是一个与注意力加工有关的结构，接受食欲素能输入。我们之前的研究表明，全身给药或直接注入基底前脑给予食欲素-1受体拮抗剂SB-334867，会破坏一项对注意力加工有明确要求的任务的表现。
鉴于食欲素-1受体与食欲素A具有高亲和力，我们测试了食欲素A是否能增强大鼠的注意力。
使用一项任务评估注意力表现，该任务要求区分可变持续时间的视觉信号与无信号呈现的试验。我们还测试了向侧脑室注入食欲素A是否能减轻基底前脑内侧前额叶皮质胆碱能投射损伤后的缺陷。
向基底前脑注入食欲素A可减轻干扰物引起的注意力表现下降。当呈现视觉干扰物时，食欲素A减轻了损伤动物的缺陷。
目前的结果支持这样一种观点，即食欲素A可通过在基底前脑的作用增强注意力表现，可能对某些因皮质胆碱能输入中断而导致注意力功能障碍的情况有益。
