Increased concentration of cerebral kynurenic acid alters stimulus processing and conditioned responding
Increased concentration of cerebral kynurenic acid alters stimulus processing and conditioned responding
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DOI：
10.1016/j.bbr.2006.03.006
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发表时间：
2006-06-30
影响因子：
2.7
通讯作者：
Bucci, David J.
中科院分区：
文献类型：
--
作者：
Chess, Amy C.;Bucci, David J.
犬尿烯酸（KYNA）是由神经胶质合成和释放的色氨酸代谢物，并且最近显示在生理相关浓度下是0烟碱乙酰胆碱受体的非竞争性拮抗剂，并且在较高浓度下是NMDA受体的非竞争性拮抗剂。KYNA浓度在患有精神分裂症和阿尔茨海默病的个体中升高，这两个群体表现出胆碱能相关的认知障碍。本研究探讨了KYNA浓度升高对大鼠条件刺激加工的影响。在实验的前2天，一组大鼠接受脑室内输注KYNA（0. 1 μ M）或载体，并返回到饲养笼或接受视觉刺激的非强化呈现。所有大鼠随后接受介绍相同的视觉刺激，然后在6天的训练阶段的食物奖励。在媒介物处理的大鼠中，预先暴露于视觉刺激减少了对光的定向行为（用后腿站立并朝向视觉刺激定向），当它后来被强化时（即，条件定向）。相比之下，预先暴露于视觉线索或2天的KYNA预处理减少了条件定向行为。最后，KYNA处理的大鼠在预暴露后的定向减少不如溶剂处理的大鼠那样稳健。这些结果表明，KYNA水平升高可以改变环境刺激的注意力处理的特定方面，并讨论了KYNA对认知功能和功能障碍的潜在贡献。(c)2006 Elsevier B.V.保留所有权利。
Kynurenic acid (KYNA) is a tryptophan metabolite synthesized and released by glia and recently shown to be a non-competitive antagonist of 0 nicotinic acetylcholine receptors at physiologically relevant concentrations, and NMDA receptors at higher concentrations. KYNA concentration is elevated in individuals with schizophrenia and those with Alzheimer's disease, two populations exhibiting cholinergic-related cognitive impairments. The present study investigated the effects of elevated KYNA concentration on conditioned stimulus processing in rats. For the first 2 days of the experiment, a subset of rats received intracerebroventricular infusions of either KYNA (0. 1 mu M) or vehicle and were either returned to the home cage or received non-reinforced presentations of a visual stimulus. All rats subsequently received presentations of the same visual stimulus followed by food reward during a 6-day training phase. In vehicle-treated rats, pre-exposure to the visual stimulus reduced orienting behaviour to the light (standing on the hind legs and orienting towards the visual stimulus) when it was later reinforced (i.e., conditioned orienting). In contrast, pre-exposure to the visual cue or 2 days of KYNA pretreatment reduced conditioned orienting behaviour. Finally, the reduction of orienting in KYNA-treated rats following pre-exposure was not as robust as in vehicle-treated rats. These results suggest that elevated KYNA levels can alter specific aspects of attentional processing of environmental stimuli and are discussed in terms of the potential contribution of KYNA to cognitive function and dysfunction. (c) 2006 Elsevier B.V. All rights reserved.