The role of peripheral cardiovascular signals in the interoceptive effects of alcohol

外周心血管信号在酒精内感受作用中的作用

• 批准号: 10592619
• 负责人: JOYCE BESHEER
• 金额: $ 39.14万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592619
• 关键词: Alcohol consumption; Alcohols; Anterior; Arousal; Behavior; Blood Pressure; Brain Stem; Cardiac; Cardiovascular system; Cues; Dizziness; Dose; Euphoria; Feedback; Genetic; Goals; Heart Rate; Homeostasis; Hunger; Interoception; Light; Lightheadedness; Midline Thalamic Nuclei; Molecular; Nausea; Nucleus solitarius; Pathway interactions; Perception; Peripheral; Procedures; Process; Rattus; Recording of previous events; Relaxation; Reuniens Thalamic Nucleus; Rewards; Role; Satiation; Signal Transduction; Source; Stimulus; Structure of rhomboidal nucleus of thalamus; Sucrose; Testing; Thalamic Nuclei; Thirst; Training; Ventral Nuclear Group; Visceral Afferents; Water; alcohol effect; conditioning; design; drinking; drug discrimination; drug of abuse; experience; experimental study; improved; indexing; insight; interest; motivated behavior; neural circuit; novel; pharmacologic; preclinical study

Abstract Interoception is the process of sensing and integrating internal signals, which is critical for maintaining bodily homeostasis. Interoceptive signals such as hunger, thirst, or arousal can thus impact behavior. Alcohol, as well as all other drugs of abuse, produces distinct interoceptive effects (i.e., lightheadedness, dizziness, relaxation). These interoceptive effects can vary dramatically by dose. Given the rich conditioning history one experiences between alcohol drinking and the interoceptive effects associated with drinking, it is important to consider that these effects could have the potential to influence drinking (signaling satiety or priming more drinking). While advances have been made in our understanding of the CNS neural circuitry and molecular mechanisms that modulate the expression of alcohol interoceptive effects, little is known regarding the role of peripheral cues to these interoceptive effects. Afferent signals from the cardiovascular system are one of the major sources of interoceptive information and as such perception of cardiac activity is a salient and central feature of interoception. To this end the goal of this application is 1) to characterize the role of peripheral cardiovascular information (heart rate and blood pressure) in the expression of the interoceptive effects of low and moderate/high alcohol doses, and 2) the functional role of the nucleus of the solitary tract (NTS), a primary brainstem target of visceral afferents in the integration of cardiovascular signals underlying alcohol interoceptive sensitivity. One of the NTS efferent targets is the nucleus reuniens (Re), a basal midline thalamic nucleus that has been relatively understudied in its role in interoception. In Aim 1, studies will assess cardiovascular signals across alcohol interoceptive training and take a pharmacological approach to directly test the functional involvement of peripheral cardiovascular signals to alcohol interoceptive effects. Studies in Aim 2 will assess the functional role of the NTS and the NTSnucleus reuniens (Re) pathway in alcohol effects and as a critical component of these cardiovascular signals. The results of the proposed studies will provide new insight into our understanding of alcohol interoceptive effects and would be the first preclinical studies to characterize peripheral cardiovascular signals in the interoceptive stimulus effects of alcohol. These findings will have broad relevance for improving our understanding of interoceptive processing and the interplay between peripheral changes and motivated behavior that is guided by alcohol interoceptive effects.

抽象的 拦截是灵敏度和整合内部信号的过程，这对于维持身体至关重要 稳态。饥饿，口渴或唤醒等互感信号因此会影响行为。酒精也是 与所有其他滥用药物一样，会产生独特的感受性影响（即头晕，头晕，放松）。 这些感受性效应可能会因剂量而巨大变化。考虑到富裕的病史 在饮酒和与饮酒相关的感受性影响之间，重要的是要考虑到 这些影响可能会影响饮酒（信号饱腹感或启动更多饮酒）。尽管 我们对中枢神经系统神经回路和分子机制的理解已经取得了进步 调节酒精际观察性效果的表达，关于外围提示的作用知之甚少 这些互感的影响。心血管系统的传入信号是主要来源之一 互感信息以及对心脏活动的感知是一个显着和核心特征 互感。为此，此应用程序的目标是1）表征外周心血管的作用 信息（心率和血压）在表达低和的互感影响方面 中等/高酒精剂量和2）固体核（NTS）的功能作用，一级 内脏传入的脑干靶标在酒精际介绍性心血管信号的整合中 灵敏度。 NTS的有效目标之一是核团圆（RE），这是一种基本的中线丘脑核，它是该核 在拦截方面的作用相对了解。在AIM 1中，研究将评估心血管信号 在酒精际观察性训练中，采取药物方法直接测试功能 周围心血管信号参与酒精际观察效应。 AIM 2的研究将评估 NTS和NTS的功能作用 - 酒精效应中的核心团聚（RE）途径，作为关键 这些心血管信号的组成部分。拟议研究的结果将为我们的新见解 了解酒精的感受性效果，这将是最早表征外围的临床前研究 酒精的互感刺激作用中的心血管信号。这些发现将具有广泛的相关性 为了提高我们对际观察处理的理解以及外围变化和外围变化之间的相互作用 受酒精际交往作用指导的动机行为。