Kynurenic Acid Regulation of Stimulus Processing

犬尿酸对刺激加工的调节

• 批准号: 7114120
• 负责人: AMY C CHESS
• 金额: $ 3.48万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114120
• 关键词: association learning; attention; auditory stimulus; behavior test; behavioral /social science research tag; brain metabolism; conditioning; cues; high performance liquid chromatography; kynurenate; laboratory rat; neural information processing; neurochemistry; neuropharmacology; nicotinic receptors; predoctoral investigator; reinforcer; sensory feedback; visual stimulus; association learning; attention; auditory stimulus; behavior test; behavioral /social science research tag; brain metabolism; conditioning; cues; high performance liquid chromatography; kynurenate; laboratory rat; neural information processing; neurochemistry; neuropharmacology; nicotinic receptors; predoctoral investigator; reinforcer; sensory feedback; visual stimulus

DESCRIPTION (provided by applicant): This proposal tests the hypothesis that elevated levels of brain kynurenic acid (KYNA) interferes with attentional processing. These studies will assess the effect of elevating endogenous KYNA on decreases in attention to an irrelevant cue in a latent inhibition task and the ability to selectively increase and decrease attention to a discrete cue in a blocking/unblocking procedure. It is predicted that elevated KYNA will prevent the normal decrease in attention to a pre-exposed stimulus, thereby reducing the latent inhibition effect and interfere with decreases in attention during blocking while leaving unblocking unaffected. These predictions are based on several lines of evidence. First, KYNA is an endogenous antagonist of the alpha7 nicotinic acetylcholine receptor, a receptor that has been implicated in attentional processing. Secondly, KYNA levels are elevated in disorders characterized by attention impairments, including schizophrenia. Specifically, persons with schizophrenia exhibit reductions in latent inhibition and blocking. In addition, recent evidence suggests that elevated KYNA can disrupt sensory gating processes, like those that are disrupted in schizophrenia, providing a compelling case for a more general role for KYNA in stimulus selection and suppression.

描述（由申请人提供）：该提案检验了以下假设：升高的脑乳元酸（KYNA）的水平会干扰注意力处理。这些研究将评估升高内源性kyna对潜在抑制任务中无关的提示的降低以及在阻塞/解除阻塞过程中选择性增加和减少对离散提示的注意力的能力。据预测，升高的Kyna将防止对预先暴露的刺激的注意力正常减少，从而降低潜在抑制作用，并干扰阻塞期间的注意力降低，同时保持未受阻止的影响。这些预测基于几条证据。首先，Kyna是α7烟碱乙酰胆碱受体的内源性拮抗剂，该受体与注意力处理有关。其次，Kyna水平的疾病升高，其特征在于注意力障碍，包括精神分裂症。具体而言，精神分裂症患者在潜在抑制和阻塞方面表现出减少。此外，最近的证据表明，升高的Kyna可以破坏感觉门控过程，例如在精神分裂症中被破坏的过程，为Kyna在刺激选择和抑制中扮演更一般的作用提供了令人信服的案例。