Differences between the nonselective adenosine receptor antagonists caffeine and theophylline in motor and mood effects: Studies using medium to high doses in animal models
Differences between the nonselective adenosine receptor antagonists caffeine and theophylline in motor and mood effects: Studies using medium to high doses in animal models
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DOI：
10.1016/j.bbr.2014.05.020
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发表时间：
2014-08-15
影响因子：
2.7
通讯作者：
Correa, Merce
中科院分区：
文献类型：
--
作者：
Lopez-Cruz, Laura;Pardo, Marta;Correa, Merce
基本原理：咖啡因和茶碱是甲基黄嘌呤，被广泛消费，有时高剂量，并作为轻微的精神兴奋剂。两者都是AI和A（2A）受体的非选择性腺苷拮抗剂，AI和A（2A）受体与纹状体区域的多巴胺D-1和D-2受体共定位。腺苷拮抗剂通常具有与多巴胺拮抗剂相反的作用。虽然咖啡因的作用广为人知，但茶碱的特征却少得多，特别是在高剂量下。方法：成年雄性CD 1小鼠用于研究广泛剂量范围的影响（25.0、50.0或100.0 mg/kg）的咖啡因和茶碱对自发运动和协调的测量，以及富含腺苷和多巴胺受体的脑区中c-Fos免疫反应性的模式。此外，我们评估了可能的焦虑和压力的影响，这些doses.Results：咖啡因，在这些剂量，受损或抑制运动在几个范例。然而，茶碱在抑制运动参数，甚至刺激运动方面不如咖啡因有效。这两种药物都能诱导皮质酮的释放，但咖啡因在中等剂量下更有效。虽然咖啡因在所有剂量下均显示出致焦虑特征，但茶碱仅在使用的最高剂量（50 mg/kg）下才表现出致焦虑特征。只有茶碱增加c-Fos免疫反应在皮质areas.Conclusion：茶碱有较少的破坏性影响比咖啡因对运动参数，并产生较少的压力和焦虑的影响。这些结果与了解高剂量服用甲基黄嘌呤的潜在副作用有关。(C)2014爱思唯尔有限公司版权所有。
Rationale: Caffeine and theophylline are methylxanthines that are broadly consumed, sometimes at high doses, and act as minor psychostimulants. Both are nonselective adenosine antagonists for AI and A(2A) receptors, which are colocalized with dopamine D-1 and D-2 receptors in striatal areas. Adenosine antagonists generally have opposite actions to those of dopamine antagonists. Although the effects of caffeine are widely known, theophylline has been much less well characterized, especially at high doses.Methods: Adult male CD1 mice were used to study the effect of a broad range of doses (25.0, 50.0 or 100.0 mg/kg) of caffeine and theophylline on measures of spontaneous locomotion and coordination, as well as the pattern of c-Fos immunoreactivity in brain areas rich in adenosine and dopamine receptors. In addition, we evaluated possible anxiety and stress effects of these doses.Results: Caffeine, at these doses, impaired or suppressed locomotion in several paradigms. However, theophylline was less potent than caffeine at suppressing motor parameters, and even stimulated locomotion. Both drugs induced corticosterone release, however caffeine was more efficacious at intermediate doses. While caffeine showed an anxiogenic profile at all doses, theophylline only did so at the highest dose used (50 mg/kg). Only theophylline increased c-Fos immunoreactivity in cortical areas.Conclusion: Theophylline has fewer disruptive effects than caffeine on motor parameters and produces less stress and anxiety effects. These results are relevant for understanding the potential side effects of methylxanthines when consumed at high doses. (C) 2014 Elsevier B.V. All rights reserved.