Department of Psychiatry, University of California San Diego, School of Medicine, MC 0714, La Jolla, CA 92093, United States of America.
Department of Psychiatry, University of California San Diego, School of Medicine, MC 0714, La Jolla, CA 92093, United States of America.
Pharmacol Biochem Behav. 2020 Apr;191:172880. doi: 10.1016/j.pbb.2020.172880. Epub 2020 Feb 24.
Caffeine is the most widely consumed psychoactive substance in the world. However, there is controversy about whether becoming addicted to caffeine is possible and a lack of well-established animal models to examine caffeine consumption. The present study sought to establish a model of caffeine consumption in Wistar rats, identify different rat populations based on caffeine preference, and determine whether extended voluntary caffeine consumption produces compulsive-like caffeine intake and withdrawal symptoms. Male Wistar rats were used throughout the experiment. The optimal concentration of caffeine to maximize caffeine consumption and caffeine preference was determined. Rats were then given continuous access to caffeine, followed by intermittent access. Rats were tested for signs of withdrawal-like behavior by measuring mechanical nociception and irritability-like behavior. Rats were further examined for compulsive-like caffeine consumption using quinine adulteration. Dose-response testing indicated an optimal caffeine concentration of 0.3 mg/mL. During intermittent access to caffeine, the rats did not escalate their caffeine intake and instead exhibited a decrease in intake over sessions. Three groups of rats were identified based on caffeine preference (high, medium, and low) across continuous and intermittent access. These three groups of rats matched low (1 cup), medium (2 cups), and high (4 cups) levels of daily coffee consumption in humans. Caffeine-consuming rats did not exhibit differences in mechanical nociception or irritability-like behavior compared with controls. In high caffeine-preferring rats but not in medium or low caffeine-preferring rats, compulsive-like caffeine consumption was observed. The present study established a rodent model of caffeine consumption that resulted in large individual differences in caffeine intake, similar to humans. Compulsive-like caffeine consumption in high caffeine-preferring rats and differences in caffeine preference between groups suggest that caffeine may result in compulsive-like intake in a subpopulation of subjects. Further testing is necessary to determine the factors that contribute to differences in caffeine preference and compulsive-like intake.
咖啡因是世界上使用最广泛的精神活性物质。然而，关于是否有可能对咖啡因上瘾以及缺乏完善的动物模型来研究咖啡因的消费，仍存在争议。本研究旨在建立一种 Wistar 大鼠咖啡因消费模型，根据咖啡因偏好确定不同的大鼠群体，并确定长期自愿摄入咖啡因是否会产生强迫性的咖啡因摄入和戒断症状。整个实验均使用雄性 Wistar 大鼠。确定了最大化咖啡因消耗和咖啡因偏好的最佳咖啡因浓度。然后，给予大鼠持续接触咖啡因，随后间歇性接触。通过测量机械性疼痛和烦躁样行为来测试大鼠是否出现戒断样行为。进一步使用奎宁掺杂物检查大鼠是否存在强迫性的咖啡因消费。剂量反应测试表明最佳的咖啡因浓度为 0.3mg/ml。在间歇性接触咖啡因期间，大鼠没有增加咖啡因的摄入量，而是在各阶段摄入量减少。根据连续和间歇性接触的咖啡因偏好，确定了 3 组大鼠（高、中、低）。这三组大鼠与人类每日咖啡摄入量的低（1 杯）、中（2 杯）和高（4 杯）水平相匹配。与对照组相比，摄入咖啡因的大鼠在机械性疼痛或烦躁样行为方面没有差异。在高咖啡因偏好的大鼠中，但在中或低咖啡因偏好的大鼠中，观察到强迫性的咖啡因消费。本研究建立了一种啮齿动物的咖啡因消费模型，该模型导致了咖啡因摄入量的个体差异很大，类似于人类。在高咖啡因偏好的大鼠中观察到强迫性的咖啡因消费，而在中或低咖啡因偏好的大鼠中则没有。这表明咖啡因可能在亚人群中导致强迫性的摄入。需要进一步的测试来确定导致咖啡因偏好和强迫性摄入差异的因素。
