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

项目摘要 味觉障碍是由患有一系列精神病理学的患者报告的，其中多巴胺是 暗示某些味觉功能可能依赖于多巴胺能信号传导。以前的报告 该提案中提出的初步数据表明，多巴胺受体拮抗剂， 血脑屏障通过降低蔗糖的适口性来减少大鼠的蔗糖摄入。虽然味道 信号具有享乐价，其与它们无条件地促进或阻止摄入的能力有关。 液体，它们也必须首先被检测。因此，得出多巴胺能调节影响 由于所感知的感官味觉信号的强度的降低也可能导致 情感潜能降低初步研究结果提供证据表明，外周注射雷氯必利，一种D2 受体拮抗剂，实际上降低了蔗糖的可检测性大鼠评估，在一个操作性 基于条件的信号检测任务，使用专门的味觉计。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。 与味觉相关的后脑区域中D2受体的存在，沿着初步数据 显示第四脑室输注雷氯必利减少蔗糖摄入，提供了一个可能的位点， 多巴胺可能对味觉引导的行为产生影响。因此，拟议的实验将 评估多巴胺D2受体激活在后脑的行为促进的必要性， 味觉的感官和情感方面。我也会评估多巴胺对感觉的影响程度 味觉功能通过探索化学特异性的影响。R 03申请中提出的研究， 这源于我在摄食行为和动物行为药理学方面的集体训练， 味觉心理物理学，将开始解开神经化学参与正常和紊乱的味觉引导 从评估多巴胺水平开始这些实验不仅有助于描述基本的 味觉功能，但它是如何在多巴胺相关的精神病理学中断，以及帮助确定潜在的 药物干预的目标，旨在遏制过量的食物摄入。这些成果 研究将作为后续R 01建议的基础，其中D2拮抗作用的位点特异性 味觉功能可通过选择性实质输注进一步检查。最终，这些实验 将指导其他神经化学系统参与正常和紊乱的味觉功能的研究。

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.