The effects of caffeine and caffeine withdrawal on mood, cognition, and fMRI.

描述(申请人提供)：咖啡因是一种广泛使用的神经刺激剂，存在于许多食物和饮料中，如咖啡、茶、软饮料和巧克力。它的高使用率意义重大，因为咖啡因对情绪、认知表现和生理指标既有急性影响，也有慢性影响。咖啡因非选择性地拮抗腺苷受体，从而既起到神经刺激剂的作用，又起到血管收缩的作用。咖啡因能明显改善情绪和注意力，减少静息的脑血流量。然而，长期使用咖啡因会导致腺苷受体上调。有证据表明，在长期使用咖啡因的人中，对神经刺激剂的影响会产生耐受性，在咖啡因戒断期间会出现头痛和疲劳等戒断症状。事实上，已经有人提出，在慢性使用者中，戒断效应的逆转超过了咖啡因的任何急性净收益。这一建议一直存在争议，因为行为文献中存在差异，有必要对咖啡因和咖啡因戒断的影响进行更全面的调查。最近，人们利用功能磁共振成像(FMRI)来研究咖啡因的作用。然而，通过拮抗血管腺苷受体，咖啡因干扰了神经活动和血流动力学反应之间的耦合。这可能会降低血氧水平依赖(BOLD)信号的峰值幅度，这与咖啡因的神经刺激作用不一致。这个问题可以通过测量大胆信号的时间进程参数来避免，因为有证据表明咖啡因减少了神经对刺激反应的潜伏期。这项拟议的研究将通过使用情绪、认知表现和生理学指标来研究咖啡因在天然咖啡因状态和戒除咖啡因30小时后的戒断状态下的影响。这个项目的具体目标将决定状态和药物效应，1)情绪和认知表现的测量，2)BOLD信号的时间进程参数，以及3)BOLD信号的行为性能和时间进程参数之间的关系。 与公共卫生相关：咖啡因是一种很好的模型药物，因为它服用起来很安全，而且滥用风险很低，但长期使用会导致耐受性和戒断症状，类似于滥用药物。作为一种模型药物，咖啡因可以增加我们对避免戒断症状如何有助于药物增强效果的理解。在这项拟议的研究中解决的问题与所有同时影响脑血流的神经活性药物有关。从这项研究中获得的信息将提高我们对咖啡因的理解，并将有助于利用药理功能磁共振研究其他药物。

DESCRIPTION (provided by applicant): Caffeine is a widely used neurostimulant that is found in many foods and beverages such as coffee, tea, soft drinks, and chocolate. Its high incidence of use is significant because caffeine has both acute and chronic effects on measures of mood, cognitive performance, and physiology. Caffeine nonselectively antagonizes adenosine receptors, thereby acting as both a neurostimulant and vasoconstrictor. Acutely, caffeine improves mood and attention, and reduces resting cerebral blood flow. However, chronic caffeine use results in an upregulation of adenosine receptors. Among chronic users there is evidence that tolerance develops to the neurostimulant effects, and withdrawal symptoms such as headache and fatigue appear during caffeine abstinence. In fact, it has been proposed the reversal of the withdrawal effects outweighs any acute net benefits of caffeine in chronic users. This proposal has been debated because discrepancies exist in the behavioral literature and a more comprehensive investigation of the effects of caffeine and caffeine withdrawal is warranted. Recently, the effects of caffeine have been studied using functional magnetic resonance imaging (fMRI). However, by antagonizing vascular adenosine receptors, caffeine interferes with the coupling between neural activity and the hemodynamic response. This may reduce the peak amplitude of the blood oxygenation level dependent (BOLD) signal, inconsistent with the neurostimulant effects of caffeine. This issue may be avoided by measuring time course parameters of the BOLD signal instead, since evidence suggests that caffeine decreases the latency of a neural response to a stimulus. The proposed study will address this by utilizing measures of mood, cognitive performance, and physiology to investigate the effects of caffeine in a native caffeinated state and a withdrawal state following 30 hours of caffeine abstinence. The specific aims for this project will determine the state and drug effects on 1) measures of mood and cognitive performance, 2) time course parameters of the BOLD signal, and 3) the relationship between behavioral performance and time course parameters of the BOLD signal. PUBLIC HEALTH RELEVANCE: Caffeine is an excellent model drug because it is safe to administer and has a low abuse liability, yet chronic use will result in tolerance and withdrawal symptoms similar to drugs of abuse. As a model drug, caffeine could add to our understanding of how the avoidance of withdrawal symptoms contributes to the reinforcing effects of drugs. The issues addressed in this proposed study are pertinent to all neuroactive drugs that simultaneously affect cerebral blood flow. The information gained from this study will improve our understanding of caffeine and will lend itself to the study of other drugs using pharmacological fMRI.