O'Neill Casey E, Levis Sophia C, Schreiner Drew C, Amat Jose, Maier Steven F, Bachtell Ryan K
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, USA.
1] Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, USA [2] Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Neuropsychopharmacology. 2015 Mar;40(4):813-21. doi: 10.1038/npp.2014.278. Epub 2014 Oct 20.
Caffeine is the most commonly used psychoactive substance, and consumption by adolescents has risen markedly in recent years. We identified the effects of adolescent caffeine consumption on cocaine sensitivity and determined neurobiological changes within the nucleus accumbens (NAc) that may underlie caffeine-induced hypersensitivity to cocaine. Male Sprague-Dawley rats consumed caffeine (0.3 g/l) or water for 28 days during adolescence (postnatal day 28-55; P28-P55) or adulthood (P67-P94). Testing occurred in the absence of caffeine during adulthood (P62-82 or P101-121). Cocaine-induced and quinpirole (D2 receptor agonist)-induced locomotion was enhanced in rats that consumed caffeine during adolescence. Adolescent consumption of caffeine also enhanced the development of a conditioned place preference at a sub-threshold dose of cocaine (7.5 mg/kg, i.p.). These behavioral changes were not observed in adults consuming caffeine for an equivalent period of time. Sucrose preferences were not altered in rats that consumed caffeine during adolescence, suggesting there are no differences in natural reward. Caffeine consumption during adolescence reduced basal dopamine levels and augmented dopamine release in the NAc in response to cocaine (5 mg/kg, i.p.). Caffeine consumption during adolescence also increased the expression of the dopamine D2 receptor, dopamine transporter, and adenosine A1 receptor and decreased adenosine A2A receptor expression in the NAc. Consumption of caffeine during adulthood increased adenosine A1 receptor expression in the NAc, but no other protein expression changes were observed. Together these findings suggest that caffeine consumption during adolescence produced changes in the NAc that are evident in adulthood and may contribute to increases in cocaine-mediated behaviors.
咖啡因是最常用的精神活性物质，近年来青少年对其消费量显著上升。我们确定了青少年摄入咖啡因对可卡因敏感性的影响，并确定了伏隔核（NAc）内可能是咖啡因诱导的对可卡因超敏反应基础的神经生物学变化。雄性Sprague-Dawley大鼠在青春期（出生后第28 - 55天；P28 - P55）或成年期（P67 - P94）饮用含咖啡因（0.3 g/l）的水或普通水28天。成年期（P62 - 82或P101 - 121）在无咖啡因的情况下进行测试。青春期饮用咖啡因的大鼠中，可卡因诱导的和喹吡罗（D2受体激动剂）诱导的运动增强。青春期摄入咖啡因还增强了在亚阈值剂量可卡因（7.5 mg/kg，腹腔注射）下条件性位置偏好的形成。在成年期饮用同等时间咖啡因的大鼠中未观察到这些行为变化。青春期饮用咖啡因的大鼠蔗糖偏好未改变，表明天然奖赏方面没有差异。青春期摄入咖啡因会降低基础多巴胺水平，并增强伏隔核中对可卡因（5 mg/kg，腹腔注射）的多巴胺释放。青春期摄入咖啡因还会增加伏隔核中多巴胺D2受体、多巴胺转运体和腺苷A1受体的表达，并降低腺苷A2A受体的表达。成年期饮用咖啡因会增加伏隔核中腺苷A1受体的表达，但未观察到其他蛋白质表达变化。这些研究结果共同表明，青春期摄入咖啡因会导致成年期伏隔核发生变化，这可能会导致可卡因介导行为的增加。
