Central Dopaminergic Modulation of Sensory and Reward Taste Function in Rats.

大鼠感觉和奖赏味觉功能的中枢多巴胺能调节。

• 批准号: 8911965
• 负责人: CLARE M MATHES
• 金额: $ 8.4万
• 依托单位: BALDWIN WALLACE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8911965
• 关键词: Affective; Animals; Behavior; Blood - brain barrier anatomy; Chemicals; Citric Acid; Corpus striatum structure; Data; Detection; Dopamine; Dopamine Antagonists; Dopamine D2 Receptor; Dopamine Receptor; Eating; Feeding behaviors; Food; Infusion procedures; Injection of therapeutic agent; Intake; Intervention; Liquid substance; Modeling; Motivation; Nucleus Accumbens; Nucleus solitarius; Operant Conditioning; Outcome; Outcome Study; Output; Patients; Pattern; Peripheral; Pharmacology; Play; Psychopathology; Psychophysics; Quinine; Raclopride; Rattus; Receptor Activation; Reporting; Research; Rewards; Role; Sensory; Signal Transduction; Site; Solutions; Specificity; Stimulus; Sucrose; Symptoms; System; Taste Disorders; Taste Perception; Testing; Training; Ventricular; Water; base; behavioral pharmacology; design; drinking; feeding; hedonic; hindbrain; motivated behavior; neurochemistry; premature; relating to nervous system; research study; response; stem

PROJECT SUMMARY Taste disturbances are reported by patients with an array of psychopathologies in which dopamine is implicated, suggesting that certain taste functions may be dependent on dopaminergic signaling. Prior reports and the preliminary data presented in this proposal show that dopamine receptor antagonists that cross the blood-brain barrier reduce sucrose intake by rats by decreasing its palatability. However, although taste signals have hedonic valence that is related to their ability to unconditionally promote or discourage intake of fluids, they also must first be detected. Thus it is premature to conclude that dopaminergic modulation impacts only taste reward since a decrease in the strength of the perceived sensory taste signal may also result in decreased affective potency. Preliminary findings provide evidence that peripheral injection of raclopride, a D2 receptor antagonist, actually decreases the detectability of sucrose by rats as assessed in an operant conditioning-based signal detection task using a specialized gustometer. These data suggest that D2 receptor antagonism directly and/or indirectly decreases sucrose taste sensitivity at a basic sensory level in a rat model. The presence of the D2 receptor in hindbrain regions associated with taste, along with the preliminary data presented showing that 4th ventricular infusion of raclopride decreases sucrose intake, provides a likely site at which dopamine may be exerting its effects on taste-guided behavior. Thus the proposed experiments will assess the necessity of dopamine D2 receptor activation in the hindbrain on behaviors facilitated by the sensory and affective aspects of taste. I will also assess the extent to which dopamine impinges on sensory taste function by exploring the chemospecificity of the effects. The research proposed in this R03 application, which stem from my collective training in both the behavioral pharmacology of ingestive behavior and animal taste psychophysics, will begin to unravel the neurochemistry involved in normal and disordered taste-guided behavior starting with an assessment of dopamine. These experiments may help characterize not only basic taste function, but how it is disrupted in dopamine-related psychopathology, as well as help identify potential targets for pharmacological interventions aimed at curbing excessive food intake. The outcomes of these studies will serve as the basis for a subsequent R01 proposal in which the site-specificity of D2 antagonism on taste function could be further examined by selective parenchymal infusions. Ultimately, these experiments will guide the study of other neurochemical systems involved in normal and disordered taste function.

项目概要 患有一系列精神病理学的患者报告了味觉障碍，其中多巴胺 暗示某些味觉功能可能依赖于多巴胺能信号传导。之前的报道 本提案中提供的初步数据表明，多巴胺受体拮抗剂可以跨 血脑屏障通过降低蔗糖的适口性来减少大鼠的蔗糖摄入量。不过，虽然味道 信号具有享乐效价，与它们无条件促进或阻止摄入的能力有关 液体，也必须首先对其进行检测。因此，现在断定多巴胺能调节影响还为时过早。 只有味觉奖励，因为感知到的感官味觉信号强度的降低也可能导致 情感效力下降。初步研究结果证明，外周注射雷氯必利（一种 D2） 受体拮抗剂，实际上降低了大鼠对蔗糖的检测能力，如在操作中评估的 使用专门的味觉计进行基于调节的信号检测任务。这些数据表明 D2 受体 拮抗作用直接和/或间接降低大鼠模型中基本感觉水平的蔗糖味觉敏感性。 后脑区域与味觉相关的 D2 受体的存在以及初步数据 提出的结果表明，雷氯必利的第四脑室输注可减少蔗糖摄入量，提供了一个可能的位点 多巴胺可能对味觉引导行为产生影响。因此，所提出的实验将 评估后脑多巴胺 D2 受体激活对行为促进的必要性 味觉的感官和情感方面。我还将评估多巴胺对感官的影响程度 通过探索效应的化学特异性来研究味觉功能。 R03 申请中提出的研究， 这源于我在摄入行为和动物的行为药理学方面的集体培训 味觉心理物理学，将开始解开涉及正常和紊乱味觉引导的神经化学 从多巴胺的评估开始的行为。这些实验不仅可以帮助表征基本特征 味觉功能，但它在多巴胺相关的精神病理学中如何被破坏，以及帮助识别潜在的 旨在抑制过量食物摄入的药物干预目标。这些结果 研究将作为后续 R01 提案的基础，其中 D2 拮抗作用的位点特异性 味觉功能可以通过选择性实质输注进一步检查。最终，这些实验 将指导涉及正常和紊乱味觉功能的其他神经化学系统的研究。