School of Experimental Psychology, University of Bristol, 12a Priory Road, Bristol BS8 1TU, UK.
Soc Cogn Affect Neurosci. 2012 Oct;7(7):831-40. doi: 10.1093/scan/nsr058. Epub 2011 Oct 4.
Caffeine, an adenosine A₁ and A(2A) receptor antagonist, is the most popular psychostimulant drug in the world, but it is also anxiogenic. The neural correlates of caffeine-induced anxiety are currently unknown. This study investigated the effects of caffeine on brain regions implicated in social threat processing and anxiety. Participants were 14 healthy male non/infrequent caffeine consumers. In a double-blind placebo-controlled crossover design, they underwent blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) while performing an emotional face processing task 1 h after receiving caffeine (250 mg) or placebo in two fMRI sessions (counterbalanced, 1-week washout). They rated anxiety and mental alertness, and their blood pressure was measured, before and 2 h after treatment. Results showed that caffeine induced threat-related (angry/fearful faces > happy faces) midbrain-periaqueductal gray activation and abolished threat-related medial prefrontal cortex wall activation. Effects of caffeine on extent of threat-related amygdala activation correlated negatively with level of dietary caffeine intake. In concurrence with these changes in threat-related brain activation, caffeine increased self-rated anxiety and diastolic blood pressure. Caffeine did not affect primary visual cortex activation. These results are the first to demonstrate potential neural correlates of the anxiogenic effect of caffeine, and they implicate the amygdala as a key site for caffeine tolerance.
咖啡因是一种腺苷 A₁ 和 A(2A)受体拮抗剂，是世界上最受欢迎的精神兴奋剂药物，但它也是一种焦虑药物。咖啡因引起焦虑的神经相关性目前尚不清楚。本研究旨在探讨咖啡因对涉及社会威胁处理和焦虑的脑区的影响。参与者为 14 名健康的男性非/低咖啡因消费者。在一项双盲安慰剂对照交叉设计中，他们在接受咖啡因（250mg）或安慰剂后 1 小时，在两个 fMRI 会话中（平衡，1 周洗脱）进行情绪面孔处理任务时，进行了血氧水平依赖性功能磁共振成像（fMRI）。他们在治疗前和治疗后 2 小时评估焦虑和精神警觉度，并测量血压。结果表明，咖啡因诱导与威胁相关的（愤怒/恐惧面孔>快乐面孔）中脑导水管周围灰质激活，并消除与威胁相关的前额皮质壁激活。咖啡因对威胁相关杏仁核激活程度的影响与饮食中咖啡因摄入量呈负相关。与威胁相关的大脑激活变化一致，咖啡因增加了自我报告的焦虑和舒张压。咖啡因对初级视觉皮层的激活没有影响。这些结果首次证明了咖啡因引起焦虑的潜在神经相关性，并且它们暗示杏仁核是咖啡因耐受的关键部位。
